Drugs help pass more ureteral stones

ILLUSTRATIVE CASE

A 52-year-old man presents to your office for follow-up 2 days after he was seen in the ED and diagnosed with a distal ureteral calculus, his first. His pain is reasonably well controlled, but he has not yet passed the stone. Is there anything you can do to help him pass the stone?

Yes. Patients who are candidates for observation should be offered a trial of “medical expulsive therapy” using an α-antagonist or a calcium channel blocker. Until now, medical therapy for kidney stones consisted of pain relief only.

The ordeal of a first stone is all too common—the lifetime prevalence of kidney stones is 5.2%—and the probability of recurrence is about 50%.^2,3

NHANES data show increasing prevalence between the periods 1976-1980 and 1988-1996.³ One fifth to one third of kidney stones require surgical intervention.⁴ In a cohort of 245 patients presenting to an ED in Canada, 50 (20%) required further procedures, including lithotripsy. Stones ≥ 6 mm in size were much less likely to pass (OR=10.7, 95% CI 4.6-24.8).⁵ The burden on the healthcare system is significant; there are approximately 2 million out-patient visits annually for this problem, and diagnosis and treatment costs about $2 billion annually.⁶

Watch and wait

The standard approach is a period of watchful waiting and pain control, with urgent urological referral for patients with evidence of upper urinary tract infection, high grade obstruction, inadequate pain or nausea control, or insufficient renal reserve.^2,4 Most patients treated with watchful waiting pass their stone within 4 weeks. Any stones that don’t pass within 8 weeks are unlikely to pass spontaneously.^2,7

Medical therapy has been proposed for decades

Medications that relax ureteral smooth muscle to help pass ureteral stones have been proposed for decades.⁸ Prior to 2000, however, only 1 randomized controlled trial (RCT) of medical therapy for ureteral stones had been published.⁹ A subsequent meta-analysis found 9 studies and showed that medical therapy did increase the chances that a stone would pass.¹⁰ The Singh meta-analysis found 13 subsequently published studies and nearly tripled the number of patients evaluated.

STUDY SUMMARY: A well-done meta-analysis

This meta-analysis is based on 16 studies of α-antagonists (most used tamsulosin) and 9 studies of nifedipine, a calcium channel blocker.¹ The studies were identified by a comprehensive search strategy that included Medline, EMBASE, and the Cochrane Controlled Trials Register from January 1980 to January 2007. The authors included all randomized trials or controlled clinical trials of medical therapy for adults with acute ureteral colic.

The authors assessed the studies for quality using the Jadad scale, a validated scale of study quality. Higher scores represent better quality, including better documentation of randomization, blinding, and follow-up. The authors specified their planned sensitivity analyses, and used the random effects model to synthesize the results, which tends to provide a more conservative estimate of the effect.

In other words, this was a very well done meta-analysis.

Twenty-two studies met the inclusion criteria: 13 of α-antagonists, 6 of nifedipine, and 3 of both. In 13 of the 16 studies of α-antagonists, tamsulosin (Flomax) was the study drug. The results from the terazosin (Hytrin) and doxazosin (Cardura) studies were included with the tamsulosin studies. The Jadad quality scores of the 22 studies were fairly low, with a median of 2 (range of 0 to 3) on the 5-point scale. The most common deduction was because the study was not double-blinded.

Medical therapy makes sense