FACTORS INFLUENCING KETOROLAC-ASSOCIATED PERIOPERATIVE RENAL DYSFUNCTION

Nonsteroidal antiinflammatory drugs (NSAIDs) are useful for the treatm ent of postoperative pain, but there is continuing concern about adver se effects on renal function. We studied the renal effects of ketorola c in an animal model using Fischer 344 rats undergoing isoflurane anes thesia and laparotomy, Treatment groups-control (C), ketorolac (5 mg.k g(-1).d(-1)) (K), large-dose ketorolac (15 mg.kg(-1).d(-1)) (KH), dehy dration-ketorolac (5 mg.kg(-1).d(-1)) (DK), gentamicin (20 mg.kg(-1).d (-1)) (G), and gentamicin (20 mg.kg(-1).d(-1)) with ketorolac (5 mg.kg (-1).d(-1)) (GK)-each comprised 10 animals. Renal function was assesse d before laparotomy and after 3 treatment days using concurrent paraam inohippurate and iothalamate clearances, respectively, to estimate ren al plasma flow and glomerular filtration rate, and by measuring serum and urine electrolytes, osmolality, urea, and creatinine. A significan t increase in serum potassium was found in the GK and DK groups. There were no major changes in renal function in the C, K, KH, and DK group s. Mild renal dysfunction was found in the G group. We found severe an d consistent changes in renal function accompanied by severe, widespre ad histological changes of acute tubular necrosis, in the GK group. In this postoperative rat model, the combination of ketorolac and gentam icin was deleterious to renal function. Implications: We examined the renal effects of the nonsteroidal antiinflammatory drug ketorolac. Ren al function was measured in rats before and after surgery and 3 days' drug administration; the kidneys studied by using microscopy. Only ket orolac plus the antibiotic gentamicin produced marked changes in kidne y function and structure.