SGEM#154: Here I Go Again, Kidney Stone

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Date: May 12th, 2016

Guest Skeptics: Dr. Tony Seupaul and Dr. Marc Phan. Tony is the Chairman of the Department of Emergency Medicine, University of Arkansas. Marc is a PGY-3 resident in the Emergency Medicine program at the University of Arkansas.

Case: 48 year old man presents to the emergency department complaining of right flank pain radiating to his groin. He states the pain comes in “waves,” and he has associated nausea without vomiting. On exam, he is afebrile and appears very uncomfortable while grabbing his right flank.

Background: We have covered renal colic a number of times on the SGEM. The last time it was a systematic review on tamsulosin from 2012. The SGEM Bottom Line from that episode was: “Tamsulosin is useless in most ED patients with ureteral colic unless their stone size exceeds at least 4mm.”

• SGEM#71: Like a Rolling Kidney Stone
• SGEM#4: Getting Un-Stoned (Renal Colic and Alpha Blockers)

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Clinical Question: Does medical expulsive therapy with tamsulosin or nifedipine increase the likelihood of spontaneous stone passage measured by the absence of need for further intervention?

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

• Population: Patients between the age 18-65 undergoing expectant management for single ureteric stone 10mm or less identified by CT
  • Excluded: Patients with suspected sepsis, GFR<30, stones >10mm and age >65yrs
• Intervention: Tamsulosin 400µg daily x 4 weeks or nifedipine 30mg daily x 4 weeks
• Comparison: placebo and each other
• Outcome:
  • Primary: Need for further treatment to achieve stone clearance in 4 weeks.
  • Secondary: Number of days for analgesic use, time to stone passage, and health status between the groups

Author’s Conclusions: “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.”

Quality Checklist for Randomized Clinical Trials:

1. The study population included or focused on those in the ED. Probably
2. The patients were adequately randomized. Yes
3. The randomization process was concealed. Yes
4. The patients were analyzed in the groups to which they were randomized. Yes
5. The study patients were recruited consecutively (i.e. no selection bias). Yes
6. The patients in both groups were similar with respect to prognostic factors. Yes
7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
8. All groups were treated equally except for the intervention. Yes
9. Follow-up was complete (i.e. at least 80% for both groups). Yes
10. All patient-important outcomes were considered. Yes
11. The treatment effect was large enough and precise enough to be clinically significant. No. 

Key Results: 1136 patients were enrolled (378 in the tamsulosin group, 379 in the nifedipine group and 379 in the control group). Mean age was in the low 40’s, 20% women, one-third of patients had a history of stones, two-thirds of stones were in the lower ureter and 75% were <5mm.

• Primary outcome: Need for additional intervention at four weeks
  • 19% for tamsulosin, 20% for nifedipine and 20% for control

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No statistical difference in spontaneous stone passage at four weeks.

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• Secondary outcomes:
  • No difference in any of the secondary outcomes for days of analgesia use, time to stone passage, and health status between groups
  • Patients used pain medication for about median of 7-10 days and the median time to stone passage was about 14 days
  • There were three serious adverse events in the nifedipine group; 1 in the placebo group

This was a large and well-done study.

1.  ED Patients: The study never explicitly stated that these patients were from the emergency department. The study simply state a routine care setting.
2. Adherence to Trial Medication: They did not verify adherence to trial medication. This weakens the conclusions that medical expulsive therapy does not work but probably is more pragmatic and representative of the “real world”.
3. Confirmation of Stone Passage: The study design did not require CT confirmation of stone passage. They rationalize this by saying ultrasound and plain films would not be accurate enough while CT scans come with a financial cost and radiation exposure. They also say that routine clinical care would involve further imaging based upon clinical concerns.
4. Patient Oriented Outcome: It could be argued that need for urologic intervention may not be the most important patient oriented outcome. Usually what patients want is to just pass the stone.
5. Secondary Outcome: Patients self reported whether or not they passed the stone and their VAS pain scores and number of days of analgesic use at four weeks. They also self reported their heath status using a questionnaire at four and twelve weeks. The response rate was only 62% at four weeks and 49% at twelve weeks. There were no measured differences between the groups who completed the survey and those who did not. However, this seriously limits the interpretation of these secondary outcomes.

Comment on author’s conclusion compared to SGEM Conclusion: We agree with the author’s conclusion that medical expulsive therapy does not change the percentage of patients that required further intervention.

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Clinical Question: What is the efficacy and safety of tamsulosin in patients with stones less than or equal to 10mm in the distal ureter?

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Reference: Furyk et al. Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial. Annals of EM 2016

• Population: Patients >18yo with symptoms suggestive of utereric colic and a calculus less than or equal to 10mm demonstrated on CT.
  • Excluded: Temperature >38C, GFR<60, stone>10mm, solidary kidney, transplanted kidney, history or ureteral strictures, know allergic reaction to study medication, current calcium channel blocker or alpha-blocker, or systolic blood pressure <100mmHg
• Intervention: 0.4mg of tamsulosin daily for 4 weeks.
• Comparison: placebo
• Outcome:
  • Co-Primary: Stone passage demonstrated on CT at 4 weeks and time to stone expulsion
  • Secondary: Unplanned re-presentation to the ED or hospital admission, total analgesia use, pain scores, need for urological intervention, complications, days off work, and adverse effects.

Authors’ Conclusions: “We found no benefit overall of 0.4 mg of tamsulosin daily for patients with distal ureteric calculi less than or equal to 10 mm in terms of spontaneous passage, time to stone passage, pain, or analgesia requirements. In the subgroup with large stones (5 to 10 mm), tamsulosin did increase passage and should be considered.”

Quality Checklist for Randomized Clinical Trials:

1. The study population included or focused on those in the ED. Yes
2. The patients were adequately randomized. Yes
3. The randomization process was concealed. Yes. All but the clinical trial pharmacist
4. The patients were analyzed in the groups to which they were randomized. Yes
5. The study patients were recruited consecutively (i.e. no selection bias). No
6. The patients in both groups were similar with respect to prognostic factors. Yes
7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes
8. All groups were treated equally except for the intervention. Yes
9. Follow-up was complete (i.e. at least 80% for both groups). Unsure
10. All patient-important outcomes were considered. Yes
11. The treatment effect was large enough and precise enough to be clinically significant. No

Key Results: n=393 (198 in the tamsulosin and 195 in the placebo group). The median age was 45years old and about 20% women. The median stone size was 4mm with about 75% being <5mm. 

• Co-Primary Outcome: Stone passage at four weeks and median time to stone passage
  • 87% tamsulosin vs. 82% placebo (difference 5% [95% CI -3.0% to 13.0%])
  • 7 days tamsulosin (95% CI 5 to 10 days) vs. 11 days placebo (95% CI 6 to 14 days)

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No significant difference in stone passage or time to stone passage.

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• Secondary Outcomes: There were no differences in any of the measured secondary outcomes (Unplanned re-presentation to the ED or hospital admission, total analgesia use, pain scores, need for urological intervention, complications, days off work, and adverse effects).
• Subgroup Analysis Stones 5-10mm:
  • 83% (30/36) tamsulosin vs. 61% (25/41) placebo
  • Difference of 22% (95% CI 3.1% to 41.6%) NNT=4.5

This was another well-done study.

1. Consecutive Patients: It was not consecutive patients and this could have introduced some selection bias into the study.
2. Co-Primary Outcomes: This is a pet peeve (co-primary or composite outcomes). It assumes both or all components are equally important. What do patients care more about, time to passage or if it passes?
3. Lost to Follow-up: The result section says 18.7% in the treatment group and 20.5% in the placebo group did not have a follow-up CT yet in the discussion they say 17%? This large number of patients missing from the primary outcome introduces another possible source of bias.
4. Compliance: This was self-reported and found to be poor. While it weakens the results of no superiority of tamsulosin vs. placebo it is probably a more accurate/pragmatic representation of what would happen in general practice.
5. Subgroup Analysis of Stones 5-10mm: They report superiority with tamsulosin but this should be interpreted with skepticism for a variety of reasons:
   • The study was designed for this subgroup analysis but they needed 98 patients in total to find an increase of stone passage from 5% to 25% with an alpha of 0.05 and a power of 0.8. They ended up only having 77 patients in total not 98.
   • Stone passage was much higher than the 5% to 25% anticipated. They observed stone passage of 61% with placebo vs. 83% with tamsulosin. This was a 22% absolute difference with an impressive NNT of 4.5.
   • Wide confidence interval around their point estimate 22% (95% CI 3.1% to 41.6%). So their point estimate is not very precise. The NNT could be as low as 2 and as high as 32.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusion that medication medical expulsive therapy is not needed for uncomplicated ureteral stones less than 10mm.

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SGEM Bottom Line: Expulsive therapy is unnecessary for ureteric stones < 5mm. There is some weak evidence that tamsulosin may help passage of larger stones (5 to 10 mm).

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Case Resolution: CT is performed and reveals a 4mm calculus in the right distal ureter. Pain is controlled with IV ketoralac and the patient is no longer feeling nauseated. Urinalysis shows no signs of infection. The patient is discharged home with pain control, expectant management and good instructions on when to return to the ED.

Clinically Application: No indication to start on medical expulsive treatment in most cases of renal colic.

What Do I Tell My Patient? You have a small 4mm kidney stone that is down near your bladder. The good news is about 80% of these stones will pass on their own. The bad news is it can take an average of 1-2 weeks for it to pass and this can be painful. However, we can treat your pain with some anti-inflammatories drugs. If that does not work you can also use some opioid pain pills as a back up plan. We will also give you some anti-nausea medications. There another medication you may hear about that has been tried called tamsulosin. It unfortunately has not show to help patients with small stones like yours <5mm in size.

Other FOAMed:

• REBEL EM: Medical Expulsion Therapy in Ureteral Colic: An Update
• emDocs: Medical Expulsion Therapy with Tamsulosin in Ureteral Colic
• CanadiEM: Knowledge Translation: SUSPEND(ing) medical expulsive therapy belief
• EM Literature of Note: Finally, an End to Tamulosin for Renal Colic?

Keener Kontest: Last weeks’ winner was Caroline Tababat-Khani from Sweden. Caroline knew that the lung point is the most specific finding for pneumothorax. Absence of lung slide alone is less specific because there are instances where patients may not have lung slide without pneumothorax (lung contusion, pleural adhesion, respiratory arrest). The lung point is a dynamic finding where the clinician actually visualized the lung coming in and out of view during respirations. It therefore represents the boarder of the pneumothorax and can be used to quantify the size of the pneumothorax (Lichtenstein  et al 2000).

Listen to the podcast for this weeks’ question. If you know the answer send it to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

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

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