Abstract
Surgical trauma triggers oxidative and inflammatory responses that contribute to postoperative complications. Although the antioxidant and anti-inflammatory effects of ketamine have been reported, the impact of anesthesia duration on these mechanisms remains unclear. Forty-two male Wistar rats were randomized into healthy control (HG), ketamine only (KET; 60 mg/kg, i.p.), or laparotomy plus ketamine with 0-4 additional ketamine doses at 20 min intervals (KET + L, KET + L1-L4). At 24 h, levels of MDA, tGSH, SOD, CAT, IL-1β, IL-6, TNF-α, adrenaline and noradrenaline were measured in tail-vein blood. One-way ANOVA with Tukey's post hoc test was used. Laparotomy under single-dose ketamine increased MDA and pro-inflammatory cytokines and decreased tGSH, SOD, CAT, ADR, and NDR versus HG and KET (all p < 0.001). After laparotomy, repeated ketamine dosing produced graded decreases in MDA and cytokines and increases in tGSH, SOD, CAT, ADR, and NDR toward control levels; effects were most pronounced in KET + L4 (all p < 0.001). Ketamine alone did not differ significantly from HG. In rats, ketamine modulates postoperative biological stress in a duration-dependent manner; prolonging anesthesia reduces oxidative-inflammatory load and restores catecholaminergic tone. These findings strongly support revisiting dose-duration protocols and underscore the need for mechanistic and clinical studies.