BACKGROUNDThe hormonal response to surgical trauma can have detrimental effects on patients. Transversus abdominis plane (TAP) block, which can improve analgesia after total abdominal hysterectomy (TAH) might attenuate the peri-operative stress response.OBJECTIVETo evaluate the ability of the TAP block to reduce stress response, opioid consumption and pain following TAH and multimodal analgesia.DESIGNRandomised, placebo-controlled double-blind study.SETTINGThe current study was conducted at a university hospital from July 2016 to September 2017.PATIENTSFifty patients scheduled for TAH were included. Anaesthesia and postoperative analgesia were standardised.INTERVENTIONAfter induction of anaesthesia, patients were allocated into two groups: ultrasound-guided bilateral mid-Axillary TAP block with 20ml of bupivacaine 0.25% (Group T) or 0.9% saline (Group C).MAIN OUTCOME MEASURESLevels of free serum cortisol, metanephrine and normetanephrine at 60min and 6, 12 and 24h after surgical incision. Pain scores and opioid consumption during the first 24h after surgery.RESULTSThere was no statistically significant difference between the median [IQR] peri-operative levels of stress hormones and pain scores between groups. Compared with baseline value 9.90 [4.2 to 23.1], free serum median cortisol levels were significantly high at 6h in Group T, 23.6 [10.1 to 42.9] P=0.015 and Group C 23.6 [9.9 to 46.3] P=0.014. Only Group C showed significant elevation from the baseline median levels of plasma metanephrine at 60min, 52.8 [33.4 to 193.2] P=0.001, 6h, 92.70 [2.4 to 202.6] P=0.005 and normetanephrine at 60min 83.44 [28.98 to 114.86] P=0.004, 6h 78.62 [36.6 to 162.31] P=0.0005 and 24h 80.96 [8.6 to 110.5] P=0.025. Mean±SD opioid consumption was similar in both groups: 39.60±14.87 in Group T vs. 43.68±14.93 in Group C (P=0.338).CONCLUSIONMid-Axillary TAP block does not improve stress response and analgesia in patients undergoing TAH receiving multimodal analgesia.TRAIL REGISTRATIONClinicalTrial.gov identifier: NCT03443271.