Introduction. Cesarean section is one of the world's most frequently performed surgical procedures. It is often accompanied by severe postoperative pain that leads to a complex immune and stress response in the body. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are reliable and readily available markers of immune response to various infectious and non-infectious stimuli. Elevated NLR and PLR values are predictive in the early detection of wound infection after cesarean section. Wound healing involves three stages: inflammation, proliferation, and remodeling. REEDA scale is a valid tool for assessing obstetric wound healing. Many factors can affect the wound-healing process. Consistent overlap between pain-related dysregulation of neuroendocrine and immune function and the aspects of the neuroendocrine and immune function shown to be critical in wound healing suggests that pain may play a role in delayed wound healing. Therefore, it is reasonable to assume that better postoperative analgesia could positively affect wound healing. According to previous research, the transversus abdominis plane (TAP) block significantly reduces pain and cortisol, epinephrine, and norepinephrine levels after cesarean section. The addition of dexmedetomidine to the local anesthetic in the TAP block has a more pronounced analgesic effect and prolongs the duration of analgesia. The investigators have found only one study that demonstrates that adding a TAP block to standard analgesia positively affects wound healing after cesarean delivery. In the literature search, investigators did not find any clinical study that has been carried out to see the influence of the addition of dexmedetomidine in TAP block on wound healing, stress response, and immune response after cesarean delivery.

We hypothesize that the use of bilateral transversus abdominis plane block after cesarean delivery will lead to lower values of the REEDA scale and attenuated stress and immune response of the patient compared to standard analgesia, where the addition of dexmedetomidine to levobupivacaine will have a more pronounced effect compared to TAP block with levobupivacaine.

Patients and methods: This prospective, randomized study will be conducted in the Department of Anesthesiology, Intensive Care Medicine and Pain Management and the Department of Gynecology and Obstetrics in the Sestre Milosrdnice University Hospital Center. A total of 120 participants will be included in the study.

The group size was obtained by power analysis. For each variable, the sample size required for cross-comparisons of the arithmetic means of the three groups was calculated using a two-tailed t-test with the power of the test β = 85%, and the level of statistical significance for each test, α = 1.667%. Standard deviations and expected differences in the arithmetic means of the examined groups were taken from the published literature. (2:24-26). The largest estimated sample size for the investigated variables is 35 subjects per group.

After the written and signed approval of the patients, they will be randomly allocated to either a control group that receives the standard postoperative analgesia (group SA) or groups that further receive the TAP block with levobupivacaine (group L), with and without the addition of dexmedetomidine (group D). All the participants will undergo elective cesarean delivery under spinal anesthesia. The classic cesarean section technique described by Pfannenstiel and Kerr technique will be performed on all the participants. The spinal anesthesia will be performed with an atraumatic spinal needle by applying height- and weight-adjusted dose of hyperbaric bupivacaine and 25 μg fentanyl intrathecally. All the participants will receive standard postoperative analgesia according to the Acute Pain Service Sestre Milosrdnice University Hospital Center (acetaminophen, tramadol, and nonsteroidal anti-inflammatory drugs). Group L and group D will additionally receive a bilateral TAP block. 20 ml of 0,25 % levobupivacaine will be administered on each side to the participants in group L and 20 ml of 0,25 % levobupivacaine with the addition of 0,5 μg/kg dexmedetomidine will be administered on each side to the participants in group D. TAP block will be performed under sterile conditions. The high-frequency linear probe will be placed transversally in the medial axillary line, and the three layers of abdominal muscles will be visualized. A 22G echogenic needle for peripheral nerve blocks will be used to inject the mixed solution in the plane between the transversus abdominis and internal oblique muscles.

Venous blood samples will be collected the day before the surgery, at 7 a.m. on the day of surgery, and at 7 a.m. on the third postoperative day. Complete blood count and serum cortisol levels will be measured. An independent observer will assess wound healing using the standardized Redness, edema, ecchymosis, discharge, and approximation (REEDA) scale 72 hours after the cesarean delivery.

Statistical analysis: The collected data for each variable will be summarized and analyzed depending on the normality of the distribution, which will be tested with the Shapiro-Wilk test. In the case of a normal distribution, the measured values will be summarized by the arithmetic mean and standard deviation. The effects of the treatment will be tested with a mixed model in which the measured value will be the dependent variable. In case of deviation from the normal distribution, the measured values will be summarized by the meridian and the first and third quartiles. Before the analysis with the mixed model they will be transformed by the inverse transformation of the ranks into the standard normal function. The calculated p-values will be considered statistically significant if they are less than 5%.