Renal response following perioperative ketorolac analgesia in living kidney donation.

Abstract

Effective postoperative analgesia involves using a combination of pharmacologic options in a multimodal approach.1-3 Therapy that combines opioids (OPIs) with nonsteroidal anti-inflammatory drugs has demonstrated a decrease in 20% to 50% of OPI use which may help improve OPI-associated nausea, respiratory depression, and constipation.4,5 Significant side effects are associated with nonsteroidal anti-inflammatory drug toxicity6 and the long-term effects of ketorolac (KET) usage in patients undergoing living donor nephrectomy (LDN) for transplantation remain unknown. We performed a retrospective analysis of patients undergoing LDN at 2 different institutions with institutional review board approval. Two hundred ninety-eight patients treated with inpatient perioperative KET (∼24 hours) (center, 1; January 3, 2001 to December 4, 2006) were compared with 163 patients that were primarily treated with post-operative OPIs (center 2; January 4, 2006 to August 5, 2013). Typically, intravenous KET was administered at the termination of the operation (15 mg × 1) and every 6 hours thereafter for 24 hours. Charts were analyzed for demographic data including age, race, sex, height, and weight. Serum creatinine (SCr) was reviewed before and at varying time points up to three years after the operation. Using SCr, % change in Cr, and estimated glomerular filtration rate (eGFR) calculated with the chronic kidney disease epidemiology collaboration equation, analysis of postdonation renal function was measured.10 Linear regression models with repeated measures compared patients managed with KET versus OPIs. These tests also analyzed interactions between treatment and demographic variables. Demographic variables between groups were studied using t tests. In addition, a power analysis was conducted for each timepoint. Mean and median follow-up were calculated based on a minimum of 3 months after the operation. Statistical analyses were performed with Statistical Analysis System (SAS Institute, Cary, NC) and R (R Development Core Team). Demographic data with SCr and eGFR across time points are demonstrated in Table 1. Patients in the OPI group were older than KET patients, but preoperative Cr was similar. Median follow-up was 365 days for KET and OPI, and mean follow-up was 430 days for KET and 381 days for OPI with a range of 3 months to 3 years. A modest but significant increase in Cr was detected in KET compared to OPI at 2 days after LDN. The average change in Cr (delta Cr) was similar between groups (0.62 vs 0.50; P = 0.05). Over time, the elevation in Cr resolved, and % change in Cr was comparable between groups at 1 week, 1 month, 1 year, and 3 years after LDN. Preoperative eGFRs were similar and exhibited comparable decreases in both groups at 2 days, 1 week, 1 month, 1 year, and 3 years after LDN.TABLE 1: Demographics, SCr, and eGFR of KET and OPITo our knowledge, this study represents the largest series with long-term follow-up examining the impact of perioperative KET on long-term renal function after LDN. In 2002, Freedland et al reported on the renal function of 83 patients 3 to 34 months after KET managed analgesia of LDN and found no immediate or long-term renal impairment with KET use for less than 48 hours. Our analysis supported that perioperative KET use was not associated with any long-term impairment in renal function after LDN compared to patients managed solely with OPIs. However, a significant increase in SCr at 48 hours postoperatively was noted with KET administration which was not seen in studies that investigated smaller study populations and shorter follow-up periods. This study has several limitations including the retrospective nature of the study, the accruement of patients at 2 different institutions with different clinical practices and parameters, and patient’s pain scores were not captured or analyzed to examine efficacy. In addition, there was a significant drop-off rate in the data captured over time (Table 1) and this affects the interpretation of our data. Future studies including improved long-term follow-up would yield a more definitive analysis. The use of multimodal postoperative pain control popularized in non-nephrectomy surgery has been applied to patients undergoing LDN. Combining analgesics that function through differing pathways has been shown to lower pain scores, lower the amount of analgesics, and result in fewer adverse events.7,8,11 In this descriptive study, use of perioperative intravenous KET was not shown to result in long-term impairment in renal function compared to patients managed by OPIs. Careful, appropriate usage of KET may be incorporated in postoperative analgesic regimens9 without deleterious effects in selected patients undergoing LDN.