Introduction: The use of ketorolac in the management of painful symptoms associated with urinary stones is well supported in the literature; however, the gastric and renal adverse effects limit the dose and duration of administration. As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help control renal colic by inhibiting smooth muscle contractions and inflammation. We sought to confirm ketorolac's inhibition of ureteral contractility and determine a dose response relationship to identify an effectiveness range.
Materials and Methods: Porcine ureter strips attached to force displacement transducers were suspended in organ tissue baths that contained aerated Krebs buffer. Tissues equilibrated for 1 hour, and a spontaneous contractility rate was established. Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM–10 μM) for 90 minutes and compared with indomethacin (1 μM) and dimethyl sulfoxide (DMSO) 0.1%. Contractility rates were recorded on a polygraph and analyzed for changes over exposure time.
Results: Ketorolac inhibition of ureteral contractility was dose dependent. At 90 minutes, the average percent decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2%; 1 nM, 34.3%; 10 nM, 56.0%; 100 nM, 69.9%; 1 μM, 88.7%; and 10 μM, 98.3%. Ureteral contractility was significantly reduced by 1 μM ketorolac (39.0%; P = 0.016) at 15 minutes when compared with DMSO. In addition, 1 μM ketorolac was not significantly different at any time point from any of the higher doses studied.
Conclusion: Ketorolac inhibition of stretch-induced ureteral contractility is concentration-dependent between 1 nM and 1 μM. Local administration of ketorolac at these doses may be useful during the management of stones while at the same time limiting the risk for adverse effects.
