In this blog we will review medical expulsive therapy (MET), or the use of medications to promote passage of a kidney stone without surgery.
CAUSES OF "STONE PAIN"The painful symptoms of an obstructing kidney stone can range from the flank to the genitals, can cause nausea, vomiting or even gastrointestinal symptoms. While the exact cause of this pain is not well understood, the pain is believed to stem from:
- obstruction - which causes distention of renal capsule, collecting system and ureter activating pain-sensing nerves in the body
- irritation - the hard, sharp stone itself can activate pain sensors
- spasm - sometimes referred to "renal colic," describes spasm of the ureter and renal collecting system that can cause contractile, episodic pain
Increasing Proximal Pressure: Hydration
Decreasing Ureteral Swelling: Anti-inflammatories
Decreasing Ureteral Contractions: Anti-spasmodicsA number of medications have been used in order to decrease ureteral spasm, improve pain and facilitate stone passage. Antimuscarinics, phosphodiesterase inhibitors and steroids have failed to demonstrate a benefit in stone passage. However, alpha-blockers (AB) and calcium-channel blockers (CCB) do improve stone passage rates and time to passage. Through direct interactions with the alpha-adrenergic receptor, AB inhibit ureteral contraction, reduce basal tone of the ureter, decrease peristaltic frequency and therefore decrease the colicky pain associated with obstruction. CCB inhibit endogenous prostaglandin synthesis and reduce spontaneous contractions of distal ureter.
Calcium Channel Blockers (CCB)
Alpha-Blockers (AB)The landmark study in AB therapy was by Pedro and colleagues in 2008. Since then, 29 studies involving over 2,000 patients have examined the role of AB for MET. A variety of AB have been used including tamsulosin, doxazosin and terazosin. The benefit for each medication ranges from a 28-56% improvement in expulsion rates. The benefit of MET with AB is significantly related to ureteral stone size. Only 4 of 9 studies with stones <5mm demonstrated a benefit in expulsion rates. However 19 of 20 studies with stones >5mm demonstrated a benefit to MET with AB. This is likely related to the very-high rate of spontaneous passage for obstructing stones <5mm without any treatment. (Interestingly, this size-to-benefit ratio is not seen in CCB, likely because fewer studies have been performed to parse out this difference).
Recommended Rx: Tamsulosin 0.4mg PO daily for 2-4 weeks or stone passed or active treatment
Side Effects of METThe most common side-effect of CCB or AB is hypotension (low blood pressure) which occurs in 0-10% of patients. However, very few patients (3-4%) stop taking the medication due to side effects and it appears that CCB are tolerated slightly better than AB for patients who develop hypotension. Importantly, these side effects are reversible with immediate discontinuation of the medication.
Benefits and Cost-Effectiveness of METThere are many proposed benefits to MET including:
- Reduced Hospitalization Rates (0-10% vs. 7-34%)
- Emergency room visits reduced (2.9 vs. 11.4)
- Work days lost reduced (2 vs. 5)
- Reduced analgesic requirements (85% studies)
- Reduced number of colic episodes (0-8% vs. 1-20%) 
- Medical Expulsion Therapy, MET can facilitate the passage of obstructing renal or ureteral stones by:
- Increasing proximal pressure
- Decreasing ureteral inflammation
- Decreasing ureteral contraction
- The best and most widely used medications include:
- Calcium-Channel Blockers
- Clinical trials demonstrate a benefit to MET:
- Increased rate of expulsion
- Decreased time to expulsion
- Low rates of side effects
- Decreased hospitalization
- Decreased narcotic requirements
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