<![CDATA[Surgical stress induces systemic inflammation characterized by increased neutrophil-to-lymphocyte ratio and interleukin-6 levels, which may contribute to postoperative pain, immune dysfunction, and complications. This systematic review aimed to evaluate the effects of preemptive ketamine administration on postoperative neutrophil-to-lymphocyte ratio and interleukin-6 levels. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Relevant studies were identified through PubMed, ScienceDirect, the Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalKey. Study selection was based on predefined population, intervention, comparison, outcome, and study-design criteria. Data were extracted using standardized tables, methodological quality was assessed using appropriate risk-of-bias instruments, and the findings were synthesized narratively according to ketamine dose, surgical procedure, biomarker measurement time, and clinical outcomes. Of 807 records identified, 17 studies were included in the final synthesis. Preemptive intravenous ketamine or S-ketamine generally reduced the early postoperative increase in the neutrophil-to-lymphocyte ratio and suppressed interleukin-6 secretion, particularly at subanesthetic doses of 0.3–0.75 milligrams per kilogram. These immunomodulatory effects were accompanied by lower postoperative pain scores, reduced opioid requirements, fewer episodes of postoperative nausea and vomiting, and a lower risk of chronic postsurgical pain. However, variations in dosage, surgical procedures, anesthetic techniques, and biomarker measurement times limited direct comparisons between studies. Preemptive ketamine appears to provide beneficial analgesic and immunomodulatory effects by attenuating postoperative systemic inflammation, although further standardized randomized trials are required to determine the optimal dosing regimen.]]>
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