A continuous infusion of ketorolac offered a safe therapeutic option for pain management after LDN or PNL. At the interim analysis, the mean pain score on the VAS for the ketorolac group was 0.6 point lower than that of the placebo group. Because this difference was smaller than the minimum criterion set forth in the power calculations in the study protocol, the study was suspended on the basis of the predetermined stopping criteria. However, we still believe that our report of these findings is an important contribution to the medical literature because it describes a novel administration of ketorolac and highlights the safety of the short-term use of this medication in patients after selected renal surgery.
We hypothesized that the use of a continuous ketorolac infusion would provide patients with a consistent steady state of medication delivery by eliminating the peaks and troughs associated with bolus dosing. This approach has been found to be effective with patient-controlled analgesia because frequent smaller doses provide smoother biodistribution and better matching of analgesic dose and patient requirement.16
Urologic studies describing the use of ketorolac for postoperative pain control are limited, and none of these studies have been double-blind, randomized, placebo-controlled trials.5-7,17-21
This is unfortunate because there can be considerable postoperative narcotic use in certain urologic populations. Lingeman et al22
reported a mean postoperative morphine use of 33.2 mg (range, 7.5-76 mg) during a mean hospital stay of 3.2 days for patients undergoing PNL. In addition, the only clinical studies that describe a continuous ketorolac infusion are in reference to cancer pain or were not randomized.4,8-10
To our knowledge, our findings are the first from a randomized, double-blind, placebo-controlled study to evaluate a continuous ketorolac infusion for postoperative pain control in patients who have undergone LDN or PNL.
Acute renal failure is a well-described complication of NSAID use. The NSAID-mediated inhibition of cyclooxygenases inhibits vasodilatory prostanoid production, thus reducing the diameter of the afferent arteriole and contributing to a decrease in the glomerular filtration rate.23
Patients with underlying volume depletion, which is common in the postoperative setting, are at risk for this phenomenon.23
We believe that adequate intravenous fluid hydration of patients receiving ketorolac is renoprotective. The use of adequate intravenous fluids to prevent intravascular dehydration may mitigate the potential detrimental effects of ketorolac on glomerular filtration rate by increasing hydrostatic pressure and volume, which may explain why no difference was observed in serum creatinine level between the ketorolac and placebo groups. A decrease was noted in the 24-hour urine output in the ketorolac group vs the placebo group (P
=.001). However, mean urine output was still excellent in both cohorts, with a mean of 142 and 175 mL/h, respectively. Furthermore, no difference was found in serum creatinine level between groups, which supports the notion that a continuous infusion of ketorolac can be used safely in the period after selected renal surgery. This finding is consistent with those in other reports in the contemporary medical literature. Freedland et al6
investigated 198 patients who underwent open LDN with or without ketorolac analgesia and found no difference at 3-month postsurgical follow-up in creatinine clearance (70% vs 73%; P
=.92) between those treated with or without ketorolac. In addition, a review of nearly 20,000 patients treated with ketorolac found that use for less than 5 days did not adversely affect renal function and resulted in no risk of renal failure.24
The use of NSAIDs may cause prostaglandin inhibition and associated platelet dysfunction that increases the risk of bleeding. The mean hemoglobin level was lower in the ketorolac group vs the placebo group on postoperative day 1 (11.5 vs 12.1 g/L; P=.01). However, no patient required a blood transfusion or returned to the operating room for bleeding, and no difference was observed in the change in the preoperative vs the postoperative hemoglobin level (1.33 vs 0.94 g/L; P=.13).
Because our study is the first to describe the use of a continuous ketorolac infusion for postoperative pain control, the power calculations were defined using a study by Schlachta et al,15
which evaluated pain control after laparoscopic colon surgery. However, the assumption that postoperative pain for renal and colon surgery would be similar, and thus a comparable effect of ketorolac on postoperative pain would be observed, may not have been accurate. In addition, in the colon study, ketorolac was provided in a bolus-dosing regimen and not as a continuous infusion as in our study. These differences in surgical technique, study design, method of drug administration, and patient populations may also account for the erroneous hypothesized pain differences used for the power calculations. Perhaps the lack of difference found in pain scores and morphine equivalents used is indicative of both the subjective nature of patient-perceived pain and the overall adequacy of postoperative pain control by the clinical pathway at our institution. In addition, perhaps our ketorolac infusion dose was too low, and thus a higher dose or infusion rate may be more effective and equally safe. Finally, perhaps our sample size, especially in the PNL group, was too small to allow us to identify a clinically meaningful difference between treatment and placebo groups.