Intraoperative methylene blue infusion reduces postoperative delirium in patients undergoing pancreatic surgery: A randomized controlled clinical trial

STUDY OBJECTIVE: Our study aims to test the hypothesis that intraoperative methylene blue reduces the incidence of postoperative delirium (POD) following major abdominal surgery, and to evaluate the inflammatory biomarkers as potential mediators. DESIGN: A randomized, single blind clinical trial. SETTING: University cancer center. PATIENTS: Three hundred and fourteen patients scheduled for pancreatic surgery. INTERVENTIONS: methylene blue within 30 min before the end of surgery, or control group, who receiving equal volume saline. MEASUREMENTS: The primary outcome was POD incidence. The secondary outcomes included plasma interleukin 6 (IL-6) and interleukin 8 (IL-8) concentrations before and after surgery, gene expressions in human brain microvascular endothelial cells (hCMEC/d3) and peripheral blood mononuclear cells (PBMCs) adhesion to hCMEC/d3. Perioperative adverse events were also documented. MAIN RESULTS: A total of 55 patients (17.5%) experienced POD, with a lower POD incidence in the methylene blue group than in the control group (11.5% vs. 23.6%, p = 0.005). The adverse events in the two groups were comparable. And postoperative plasma IL-6 but not IL-8 concentration was lower in the methylene blue group. Furthermore, endothelial TNF-α, MCP-1 and VCAM1 expressions were lower when treated with serum from the methylene blue group, and the number of PBMCs adhesion to hCMEC/d3 cells was also less in the methylene blue group. CONCLUSION: Intraoperative methylene blue use effectively and safely reduced the POD incidence in patients undergoing pancreatic surgery, which may be associated with decrease in systemic inflammation and immunovascular interactions.