A Double-Blind Randomized Controlled Trial of Continuous Intravenous Ketorolac vs Placebo for Adjuvant Pain Control After Renal Surgery

doi:10.1016/j.mayocp.2012.07.018

Mayo Clinic Proceedings

Volume 87, Issue 11, November 2012, Pages 1089-1097

https://doi.org/10.1016/j.mayocp.2012.07.018 Get rights and content

Abstract

Objective

To evaluate the efficacy and safety of a novel, continuous intravenous infusion of ketorolac, a powerful nonopioid analgesic, for postoperative pain control.

Patients and Methods

A prospective, double-blind, randomized, placebo-controlled trial of a continuous infusion of ketorolac tromethamine in 1 L of normal saline vs placebo was performed in 135 patients aged 18 to 75 years after laparoscopic donor nephrectomy or percutaneous nephrolithotomy completed from October 7, 2008, through July 21, 2010. Primary study end points were the 24-hour differences in visual analog pain scores and total narcotic consumption, whereas secondary end points were differences in urine output, serum creatinine level, and hemoglobin level.

Results

The study was stopped after randomization of 135 patients (68 in the ketorolac group and 67 in the placebo group) when interim analysis indicated that the difference in mean pain scores between the 2 groups (difference, 0.6) was smaller than the 1-point threshold set forth in the power calculations. No statistically significant change was noted in hemoglobin levels from preoperative to postoperative values (P=.13) or in postoperative serum creatinine levels (P=.13).

Conclusion

Although continuous infusion of ketorolac produced only a modest decrease in the use of narcotics, it appears to offer a safe therapeutic option for nonnarcotic pain control.

Trial Registration

clinicaltrials.gov Identifiers: NCT00765128 and NCT00765232

Section snippets

Patients

After approval from the Mayo Clinic Institutional Review Board, we conducted a prospective, double-blind, randomized, placebo-controlled trial of ketorolac vs placebo for postoperative pain control in LDN and PNL patients treated at the Mayo Clinic Hospital in Phoenix, Arizona, from October 7, 2008, through July 21, 2010. Men and women aged 18 to 75 years who were undergoing LDN or PNL were candidates for participation. Exclusion criteria included pregnancy, inability to provide informed

Results

We prospectively identified a total of 218 patients who were scheduled to undergo either LDN or PNL at our hospital. Twenty-seven patients were not eligible because of exclusion criteria, 51 declined consent, and 4 did not order the study in time, leaving a total of 135 patients who were randomized to ketorolac (n=68) or placebo (n=67) (Figure 2). Seven patients who consented did not complete the study because the planned procedure was not performed (6 patients) or because ketorolac was given

Discussion

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

Conclusion

Ketorolac appears to offer a safe therapeutic option for patients in the acute postoperative period after LDN or PNL, with no differences seen in serum creatinine level or changes in hemoglobin level between groups. Although the decreased use of narcotics was only modest, to our knowledge, this study is the first randomized, double-blind, placebo-controlled trial to highlight the novel approach of providing a continuous steady state of ketorolac. As such, it represents the highest level of

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Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain: a double-blind, placebo-controlled, multicenter study

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Cited by (20)

Prospective, double-blind, randomized clinical trial comparing an ERAS pathway with ketorolac and pregabalin versus standard of care plus placebo during live donor nephrectomy for kidney transplant
2019, American Journal of Transplantation
Opioid exposure is a concern after live donation for kidney transplant. We theorized that an enhanced recovery after surgery pathway (ERAS) using pregabalin preoperatively to desensitize nerves followed by the nonsteroidal anti-inflammatory drug ketorolac, during and after surgery, can control pain, thus requiring less perioperative narcotics. The aim of this study was to determine if the use of a nonopioid analgesic ERAS protocol for donor nephrectomies could decrease the use of narcotics without an increase in complications compared with standard of care (SOC). This is a single-center, prospective, double-blind, randomized clinical trial involving a total of 62 patients undergoing nephrectomy for live donor kidney transplant. Length of hospital stay (LOS) was significantly reduced by 10% in the ERAS group versus the SOC-plus-placebo group. Morphine dose equivalents were significantly reduced by 40% in the study group versus the SOC-plus-placebo group. The use of this nonopioid analgesic ERAS pathway for donor nephrectomies decreased the use of narcotics without an increase in complications compared with SOC. There was significantly reduced LOS and less narcotic use in the study group versus the SOC-plus-placebo group. (ClinicalTrials.gov registration number: NCT03669081).
TORPEDO: Prospective, double blind, randomized clinical trial comparing the use of Ketorolac verse placebo during live donor nephrectomy for kidney transplant
2017, Transplantation Reports
Citation Excerpt :
Prostaglandins are needed to dilate the afferent arteriole; NSAIDs effectively reverse this. The patients at highest risk are those with fluid imbalances or with compromised renal function (e.g., heart failure, diuretic use, cirrhosis, dehydration, and renal insufficiency) [12,13]. There are multiple retrospective reviews from transplant centers attempting to debunking this theory; however, there is no prospective level one evidence allowing for definitive resolution of this conflict [14].
The aim of this pilot study was to determine if the use of Ketorolac for donor nephrectomies could decrease the use of narcotics. Methods: This is a prospective, double blind, randomized trial involving patients undergoing nephrectomy for live donor kidney transplantation. Three arms: 1. Ketorolac 30 mg IV×1 in the OR, then ketorolac 15 mg IV every 6 h for 7 doses. 2. Ketorolac 30 mg IV×1 in the OR, then placebo IV every 6 h for 7 doses. 3. Placebo IV×1 in the OR, then placebo IV every 6 h for 7 doses. Outcomes: blood loss, mortality, renal function, cumulative narcotic use, length of hospital stay (LOS), and urinary retention. Results: There were no patient deaths, blood transfusions or renal dysfunction in any study arm. Arm 1 had less narcotic use, reduced length of stay, and reduced urinary retention than Arm 3. Conclusion: There was reduced LOS, less narcotic use and less urinary retention in the Ketorolac group (Arm 1) versus the placebo group (Arm 3). Based on these results we will proceed with a larger study to compare the use of non-opioid analgesics in donor nephrectomies.
Long-term renal function after donor nephrectomy: Secondary follow-up analysis of the randomized trial of ketorolac vs placebo
2014, Urology
Citation Excerpt :
This study has several limitations. The present study is a follow-up analysis of a previously conducted randomized controlled trial of ketorolac in renal surgery patients.7 As such, it was not specifically powered to assess long-term renal function in donor nephrectomy patients; however, the information on the safety of the use of ketorolac warrants exploration in this population.
To evaluate the long-term safety of a novel continuous infusion of ketorolac vs placebo after laparoscopic donor nephrectomy.
We performed a secondary analysis of a previously reported randomized controlled trial conducted from October 7, 2008, to July 21, 2010. Patients aged 18-75 years received a continuous infusion of either ketorolac (treatment [n = 57]) or normal saline (control [n = 54]) for 24 hours immediately after laparoscopic donor nephrectomy. Serum creatinine levels were measured at 1- and 1.5-year follow-ups. Glomerular filtration rate was calculated preoperatively, postoperatively, and at 1- and 1.5-year follow-ups using the Chronic Kidney Disease Epidemiology Collaboration equation. Glomerular filtration rates were compared between treatment and control groups using 2-sample t tests.
Data analysis for the 111 donor nephrectomy patients showed that glomerular filtration rates decreased in both groups over time, but changes were not clinically significant. No difference was found in glomerular filtration rates (in mL/min/1.73 m²) between treatment and control groups at 1-year follow-up (89.29 vs 87.94 mL/min/1.73 m²; P = .58) or at 1.5-year follow-up (88.54 vs 90.25 mL/min/1.73 m²; P = .51).
The novel provision of continuous steady-state ketorolac is safe for postoperative pain control in patients after donor nephrectomy, with no change in glomerular filtration rates between treatment and control groups acutely and at up to 1.5-year follow-up.
Neostigmine and ketorolac as adjuvants to local anesthetic through peribulbar block in patients undergoing vitrectomy surgeries: A randomized controlled trial
2022, Egyptian Journal of Anaesthesia
Comparative study between the analgesic effect of ketorolac when administrated intravenous preoperatively versus when added to local anesthesia in squint surgery
2022, Egyptian Journal of Anaesthesia
Adjuvant ketorolac to peribulbar anesthesia in cataract surgery: a comparative study
2021, Delta Journal of Ophthalmology

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: Grant Support: This project was funded by a CR5 Mayo Clinic grant.

: Potential Competing Interests: Dr Castle is a speaker for Intuitive Surgical Inc. Dr Humphreys has a consulting agreement with Boston Scientific Corp, Lumenis Inc, and Medafor Inc. Mr Hentz has received grant support for research activity from Allergan Inc, Anodyne Therapy LLC, Astellas Pharma US Inc, Dynatherm Medical Inc, Genentech Inc, InKline Pharmaceuticals Inc, Medtronic Inc, and Millennium Pharmaceuticals Inc.

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Original articleA Double-Blind Randomized Controlled Trial of Continuous Intravenous Ketorolac vs Placebo for Adjuvant Pain Control After Renal Surgery

Abstract

Objective

Patients and Methods

Results

Conclusion

Trial Registration

Section snippets

Patients

Results

Discussion

Conclusion

J Urol

Urology

Urology

J Pain Symptom Manage

Am J Emerg Med

J Urol

J Urol

J Urol

J Urol

Pain as a factor complicating recovery and discharge after ambulatory surgery

Anesth Analg

Evaluation of intravenous ketorolac administered by bolus or infusion for treatment of postoperative pain: a double-blind, placebo-controlled, multicenter study

Anesthesiology

Original article
A Double-Blind Randomized Controlled Trial of Continuous Intravenous Ketorolac vs Placebo for Adjuvant Pain Control After Renal Surgery