Effects of ketorolac on renal blood flow and function during hemorrhagic hypotension in dogs under spinal anesthesia

Ketorolac, a non-steroidal anti-inflammatory drug, has gained widespread use in management of postoperative pain. Impairment of renal function is a known adverse effect of ketorolac, considered to be due to inhibition of prostaglandin (PG) synthesis in the kidney1. The generation of local PGs in the kidney serves as a counterbalance to other hormonal influences and acts to maintain normal renal function in the face of disease or circulatory stress. Very little information exists quantifying the effects of ketorolac on renal function during the combination of regional anesthesia and circulatory stress. We therefore decided to study that in a chronically instrumented dog model. Methods: The protocol was approved by the institutional animal care committee. Renal function was studied in six mongrel dogs with chronically implanted renal artery flow probes and aortic, urinary bladder and spinal catheters. Each animal was studied on two separate occasions: resting awake, during lidocaine spinal anesthesia, hemorrhagic hypotension (30% of estimated blood volume removed during 30 minutes) and 20 and 60 minutes after reinfusion of the removed blood. Ketorolac 1.5 mg/kg i.m. was randomly administered before one of the two occasions. Renal blood flow (RBF), GFR (inulin clearance), sodium excretion, urine flow rate, mean arterial pressure (MAP), and plasma levels of renin and catecholamines were measured during each stage of the experimental protocol. Post event controls were obtained within one week. ANOVA was used for statistical analysis. Results: RBF was unchanged after institution of spinal anesthesia in both groups. RBF fell by 38% in the ketorolac group after hemorrhage (p<0.05) but remained unchanged in the untreated group. GFR decreased in both groups after hemorrhage. The decrease was significantly larger in the ketorolac treated animals. RBF and GFR returned to control after reinfusion of blood. MAP did not differ between groups during the different experimental situations. Discussion: These data suggest that ketorolac impairs the kidney's ability to compensate for circulatory stress during spinal anesthesia. This needs to be considered when ketorolac is used in patients with impaired renal function or in situations where renal function is at risk.