General vs. Regional anesthesia: differential effects on postoperative anxiety, depression, and stress biomarkers in arthroscopic knee surgery: a randomized clinical trial

Objective: To compare the effects of general anesthesia (GA) and regional anesthesia (RA) on postoperative anxiety and/or depression (PAD) in patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR), and explore potential mediation by salivary cortisol (SC) or alpha-amylase (sAA). Methods: This prospective, randomized trial compared GA versus RA in 82 patients undergoing ACL reconstruction. Primary Outcomes were incidences of PAD, SC, sAA, and blood glucose levels. Secondary Outcomes: knee swelling, skin temperature, postopeative opioid consumption, Numeric Rating Scale (NRS) pain scores, hospital stay, and hospitalization costs. Assessments were conducted at 1d preoperatively (T0), surgery day (T1), postoperative 2 h (T2), 1d (T3), 2d (T4), and 5d (T5). Results: After adjusting for all confounding factors combined (anesthesia preference, preoperative NRS pain scores and baseline HADS scores), the incidence of postoperative anxiety was significantly higher in the RA group compared to the GA group at T3 (p < 0.000), T4 (p = 0.001), and T5 (p = 0.001). In contrast, SC levels were significantly higher in the GA group than in the RA group at T2 (p < 0.001), T3 (p = 0.010), and T4 (p = 0.012). Mediation analysis revealed a non-significant indirect effect of salivary cortisol (SC) on the relationship between anesthesia technique and postoperative anxiety. No significant differences were observed in postoperative depression, sAA activity, or blood glucose levels between groups. Conclusions: GA exhibits lower postoperative anxiety in ACLR patients, whereas RA shows superior perioperative SC suppression. SC did not mediate the relationship between anesthesia technique and postoperative anxiety. These findings suggest GA may benefit anxiety-prone individuals, while RA appears advantageous for stress-sensitive cases.