Effect of minimal flow anesthesia on oxidative and neuroendocrine stress responses

Introduction and Aim: Minimal flow anesthesia is a safe and effective technique that provides physiological benefits while offering significant economic and environmental advantages. Modern anesthesia devices are designed to ensure the safe administration of this technique. The anesthesia method used during surgery, along with the duration and approach of the procedure, can influence immune function and lead to an increase in reactive oxygen species (ROS). Additionally, surgical trauma triggers the release of inflammatory markers and stress hormones via the sympathetic nervous system, potentially contributing to postoperative complications. Reducing oxidative stress and the neuroendocrine stress response can accelerate recovery and minimize postoperative complications. Therefore, understanding the effects of anesthetic agents on surgical stress is of critical importance. This prospective randomized study aimed to compare minimal flow (0.4-0.5 L/min) and high-flow (4 L/min) anesthesia in patients undergoing septorhinoplasty in terms of interleukin-6 (IL-6) levels, adrenocorticotropic hormone (ACTH), cortisol, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) values, hemodynamics, surgical field bleeding levels, and recovery scores. Materials and Methods: This study was designed as a randomized controlled prospective study involving patients aged 18-65 years with an American Society of Anesthesiologists (ASA) score of 1-2 who were scheduled for elective septorhinoplasty. A total of 35 patients were included, all of whom received standard anesthesia induction. Patients were randomly assigned into two groups: the high-flow group (4 L/min, Group HF, n=18) and the minimal-flow group (0.5 L/min, Group MF, n=17). Sevoflurane anesthesia was maintained at a minimum alveolar concentration (MAC) of 1.0-1.2 in both groups, and all patients received remifentanil infusion. Blood samples were collected at four time-points: after induction (T1), at the end of the operation (T2), at postoperative 6th hour (T3), and at postoperative 18th hour (T4). The primary outcome was the analysis of interleukin-6 (IL-6) levels at t1, t3, and t4. Secondary outcomes included adrenocorticotropic hormone (ACTH), cortisol, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values, intraoperative sevoflurane consumption, hemodynamics (heart rate, mean arterial pressure, SpO2, body temperature), surgical field bleeding scores (Boezaart Scoring System and surgical satisfaction survey), postoperative visual pain scores, and nausea-vomiting severity at postoperative 6th and 18th hours. Patients were monitored in the postoperative care unit for 30 minutes, during which visual pain scores, Aldrete scores, and nausea-vomiting scores were recorded. Results: Demographics (age, gender, BMI), smoking history, comorbidities, durations of anesthesia and surgery, as well as intraoperative and postoperative hemodynamic parameters were similar between the groups. IL-6, ACTH, and cortisol levels did not show statistically significant differences between the groups at any time-point. The TOS level at t1 was significantly higher in Group MF (8.65) than in Group HF (6.18) (p=0.035). TAS levels at t2 and t3 were significantly higher than at t1 in both groups (Group HF: p<0.001, p=0.008; Group MF: p<0.001, p=0.005). In Group MF, TOS levels at t3 (35.5) were significantly higher than at t4 (8.12) (p=0.002). In Group HF, ACTH levels at t1 (17.83) were significantly higher than at t3 (7.45) and t4 (5.94) (p=0.001, p=0.004). In Group MF, ACTH levels at t1 (27.89) were significantly higher than at t3 (11.12) and t4 (9.93) (p<0.001, p<0.001). In Group HF, cortisol levels at t1 (18.67) were significantly higher than at t2 (7.13), t3 (6.00), and t4 (3.06) (p=0.034, p=0.003, p<0.001). In Group MF, cortisol levels at t1 (21.57) were significantly higher than at t3 (3.96) and t4 (2.47) (p=0.017, p<0.001). No significant differences were found in Boezaart scores or surgical satisfaction surveys between groups. Sevoflurane consumption was significantly lower in Group MF (Group HF: 20.93 ml, Group MF: 25.62 ml, p<0.001). The fresh gas oxygen percentage was significantly higher in Group MF (Group HF: 4 L/min, Group MF: 0.41 L/min, p<0.001). No significant differences were observed between groups in Aldrete scores (p>0.05), nausea-vomiting scores (p=0.72), or VAS scores (p=0.44) within the first 24 hours. Conclusion: Minimal flow anesthesia demonstrated similar effects to high-flow anesthesia regarding neuroendocrine stress markers (IL-6, ACTH, and cortisol) and oxidative stress parameters (TAS, TOS, and OSI). Minimal flow anesthesia is safe method in terms of stress markers, hemodynamic and respiratory parameters, surgical satisfaction, and recovery scores. Keywords: Interleukin-6, Minimal flow anesthesia, oxidative stress, neuroendocrine stress response, sevoflurane