Evaluation of pre-operative high dose corticosteroids in elective colorectal surgery and effects on gut barrier function: A phase 2 clinical trial

Background Perioperative inflammation is a predictor of surgical complications and cancer prognosis in surgical oncology. Multimodal protocols are ongoing in order to find ways to control inflammation. A preoperative flash high-dose of corticosteroids has been suggested as a way to control perioperative inflammation, but its safety in colorectal surgery needs to be established prior to a phase 3 trial. The physiologic effects of such a dose should also be explored. Methods Prospective bicentric phase 2 single-arm study with a biological ancillary study. Patients were administered 20 mg/kg of methyl-prednisone before colorectal surgery. Primary outcome was major post-operative complications defined as a grade >II according to the Dindo-Clavien classification. Ancillary outcome was plasma endotoxin concentration and activity. Results Sixty-seven patients were included. Twelve (17.9 % [90 %CI:10.9 %-29.6 %]) patients developed major post-operative complications. No homeostatic disturbances troubles were observed. Severe postoperative hyperglycemia concerned 3 (4 %) patients which were all non-diabetic. The concentrations of endotoxin (mass) and its activity lowered between the pre-operative time point and the day after surgery. Conclusion Pre-operative single flash of high dose methylprednisolone (20 mg/kg) before elective colorectal surgery seemed safe. Our results suggest that corticosteroids could promote gut barrier integrity, reducing endotoxemia in patients with colorectal surgery. Further studies (in particular a large randomized controlled trial) are needed to confirm our findings and explore a potential benefit of corticosteroid in this population. ClinicalTrials.gov 03437746