The effect of low-dose ketorolac on minimally invasive transforaminal lumbar interbody fusions: final analysis of a randomized, double-blinded, placebo-controlled trial.

Abstract

In this study, the authors aimed to evaluate the safety and efficacy of short-term, low-dose ketorolac following minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) with bone morphogenetic protein (BMP), specifically assessing its impact on fusion rates and postoperative opioid consumption in a randomized, double-blind, placebo-controlled, noninferiority trial. Adult patients undergoing elective 1- to 3-level MIS TLIF with BMP between October 2017 and April 2024 were randomized to receive perioperative ketorolac or placebo in addition to a standardized multimodal analgesic regimen. The primary outcome was radiographic fusion at 1 year, assessed by independent neuroradiologists using dynamic radiographs and CT scans as needed. A noninferiority margin of -0.15 was prespecified. Secondary outcomes were 48-hour and total in-hospital opioid consumption (intravenous morphine milligram equivalents [MME]) and length of stay (LOS). Patient-reported outcomes (PROs) were collected at baseline and postoperative intervals. Analyses were performed per protocol with significance set at an α value of 0.025. Of 420 randomized patients, 31 in the ketorolac group and 34 in the placebo group were excluded due to surgery cancellation, protocol violations, or withdrawal of consent. One hundred sixty-seven patients remained in the ketorolac group and 188 in the placebo group. The per-protocol analysis included 364 levels (1 year) and 395 levels (2 years) for fusion assessment, and 355 patients for secondary outcomes (MME and LOS). Baseline demographics and intraoperative characteristics were comparable between groups. The fusion rate did not significantly differ at 6 months (Δ = 0.8, 95% CI -5.6 to 7.1; p = 0.51), 1 year (Δ = 2.5, 95% CI -3.4 to 8.2; p = 0.39), or 2 years (Δ = 2.6, 95% CI -2.6 to 7.7; p = 0.49). The lower bounds of the 95% confidence intervals for differences in solid fusion rates did not cross the -0.15 noninferiority margin at any time point, confirming the noninferiority of ketorolac. The mean total in-hospital MME (Δ = 22.65, 95% CI 12.27-33.04; p < 0.001) and 48-hour MME (Δ = 17.19, 95% CI 9.24-25.13; p < 0.001) were significantly reduced in the ketorolac group. Patients receiving ketorolac demonstrated significantly lower mean visual analog scale pain scores over the first 48 hours (Δ = 0.52, 95% CI 0.18-0.86; p = 0.003) and shorter LOS (Δ = 0.73 days, 95% CI 0.39-1.07 days; p < 0.001). There were no significant differences in complications, revision surgery, or PROs. Short-term, low-dose ketorolac following MIS TLIF with BMP maintained noninferior fusion rates while providing significant reductions in opioid requirements, hospital stay, and early postoperative pain. Clinical trial registration no.: NCT03278691 (ClinicalTrials.gov).