This study aimed to evaluate the analgesic effects and safety of multidrug cocktail injections for postoperative pain management in patients undergoing lumbar microendoscopic decompression surgery. A prospective randomized controlled trial was conducted with 70 patients who underwent lumbar microendoscopic decompression surgery between December 2023 and May 2024. Patients were randomly assigned to receive either a multidrug cocktail injection (cocktail group, n = 35) or no cocktail injection (non-cocktail group, n = 35). Primary outcomes included scores of the numerical rating scale (NRS) for pain from postoperative days 1 to 7 and the number of analgesics used within the first 3 postoperative days. Secondary outcomes included sex, age, body mass index, preoperative diagnosis, surgical levels, duration of surgery, blood loss, C-reactive protein (CRP) levels on postoperative day 1, and drain output. The cocktail group experienced significantly lower pain levels from postoperative days 1 to 7 (p < 0.05) and used fewer analgesics within the first 3days (p = 0.01) compared with the non-cocktail group. Additionally, the cocktail group had significantly lower CRP levels (p < 0.001) and a shorter hospital stay (p = 0.01). No significant differences were observed in the duration of surgery, blood loss, or drain output between the groups. Multidrug cocktail injections are effective and safe for postoperative pain management in lumbar microendoscopic decompression surgery, significantly reducing pain, analgesic use, CRP levels, and hospital stay. These findings suggest that incorporating multidrug cocktail injections into postoperative care protocols can enhance patient recovery and outcomes.
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