Factors influencing ketorolac-associated perioperative renal dysfunction.
Nonsteroidal antiinflammatory drugs (NSAIDs) are useful for the treatment of postoperative pain, but there is continuing concern about adverse effects on renal function. We studied the renal effects of ketorolac in an animal model using Fischer 344 rats undergoing isoflurane anesthesia and laparotomy. Treatment groups--control (C), ketorolac (5 mg x kg(-1) x d(-1)) (K), large-dose ketorolac (15 mg x kg(-1) x d(-1)) (KH), dehydration-ketorolac (5 mg x kg(-1) x d(-1)) (DK), gentamicin (20 mg x kg(-1) x d(-1)) (G), and gentamicin (20 mg x kg(-1) x d(-1)) with ketorolac (5 mg x kg(-1) x d(-1)) (GK)--each comprised 10 animals. Renal function was assessed before laparotomy and after 3 treatment days using concurrent paraaminohippurate and iothalamate clearances, respectively, to estimate renal plasma flow and glomerular filtration rate, and by measuring serum and urine electrolytes, osmolality, urea, and creatinine. A significant 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 groups. Mild renal dysfunction was found in the G group. We found severe and consistent changes in renal function, accompanied by severe, widespread histological changes of acute tubular necrosis, in the GK group. In this postoperative rat model, the combination of ketorolac and gentamicin was deleterious to renal function.


CONCLUSIONS
We examined the renal effects of the nonsteroidal antiinflammatory drug ketorolac. Renal function was measured in rats before and after surgery and 3 days' drug administration; the kidneys studied by using microscopy. Only ketorolac plus the antibiotic gentamicin produced marked changes in kidney function and structure.
Jaquenod
M
M
Department of Anaesthesia and Pain Management, University of Sydney at the Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
Rönnhedh
C
C
Cousins
M J
MJ
Eckstein
R P
RP
Jordan
V
V
Mather
L E
LE
Power
I
I
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006947:Hyperkalemia / Q000139:chemically induced; D020910:Ketorolac; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014046:Tolmetin; D020910:Ketorolac