BACKGROUND: Ketorolac is widely utilized for postoperative pain management, including back pain after lumbar spinal surgery. Several trials have assessed the efficacy of Ketorolac alone and in combination with other analgesics such as bupivacaine, morphine, epinephrine, paracetamol, and pregabalin. However, the effects and safety profile of ketorolac in these contexts remain controversial.
OBJECTIVE: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of Ketorolac administration, both as a monotherapy and in combination with other analgesics, for managing postoperative pain in adults undergoing lumbar spinal surgery.
METHODS: We searched PubMed, EMbase, Web of Science, EBSCO, CNKI, WanFang, VIP, and Cochrane library databases through July 2024 for randomized controlled trials (RCTs) assessing the analgesic efficacy of Ketorolac administration for postoperative pain of lumbar surgery. The meta-analysis was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statements. Data were extracted and analyzed using open-source meta-analysis software OpenMeta-Analyst, focusing on outcomes such as VAS pain scores, postoperative morphine requirements (PMR), length of hospital stay (LOS), and adverse effects, such as nausea, vomiting, pruritus, and constipation. The quality of evidence was assessed using the Jada scale.
RESULTS: Thirteen RCTs comprising a total of 938 patients were included. The methodological quality of the studies was high, with three studies scoring 5, six studies scoring 4, and four studies scoring 3 on the Jadad scale. Ketorolac significantly reduced pain compared to controls at 0-6 h, with a mean difference (MD) of - 1.42 (95% CI: - 2.03 to - 0.80; P < 0.0001), exceeding the Minimal Clinically Important Difference (MCID) of 1.2 to 2.0 points on the Visual Analog Scale (VAS), indicating clinically meaningful pain relief. During the 6-12-h period, the pain reduction was significant (MD =  - 0.58; 95% CI: - 0.80 to - 0.35; P < 0.0001), though below the MCID threshold. In the 12-24-h period, Ketorolac continued to show significant pain reduction (MD =  - 0.48; 95% CI: - 0.68 to - 0.28; P < 0.0001), but this reduction was also below the MCID. Heterogeneity was low in the 12-24-h period (I2 = 13%), indicating consistent results across studies. There was a significant reduction in PMR (SMD =  - 1.83; 95% CI =  - 3.42 to - 0.23; P < 0.0001), although with considerable heterogeneity among the studies (I2 = 93%, heterogeneity P < 0.01). Ketorolac administration also significantly reduced the LOS compared to controls (MD =  - 0.45 days; 95% CI =  - 0.74 to - 0.16; P = 0.0001), though this reduction, which is less than a full day (0.45 days), may have limited clinical significance. The findings suggest that Ketorolac effectively reduces pain and opioid use postoperatively, supporting its role in multimodal analgesia for lumbar spinal surgery. The significant reduction in PMR indicates a beneficial opioid-sparing effect, crucial in the context of reducing opioid-related complications. The observed reduction in LOS, while statistically significant, may not translate into substantial clinical benefit due to its limited magnitude. No significant increase in common adverse effects was noted, indicating Ketorolac's safety profile.
CONCLUSION: Ketorolac administration, either alone or in combination with other analgesics, effectively reduces postoperative pain and opioid consumption in adults following lumbar spinal surgery. And Ketorolac did not significantly increase the incidence of postoperative nausea and vomiting relative to other analgesics or placebos. While it also decreases LOS, the clinical relevance of this reduction is modest. However, the variability in study designs, dosages, and combination therapies contribute to significant heterogeneity in outcomes. Future research should focus on standardizing protocols and exploring optimal dosing strategies. Additionally, long-term safety and effectiveness studies are needed to better understand Ketorolac's role in postoperative pain management.