The Effects Of Perioperative Dexamethasone On Eicosanoids And Mediators Of Inflammation Resolution: A Sub-Study Of The Paddag Trial

Introduction: Dexamethasone is an antiemetic that is frequently administered before or after the induction of anesthesia for prevention and treatment of perioperative nausea and vomiting. Dexamethasone has anti-inflammatory and immunosuppressive effects primarily via suppression of expression of inflammatory mediators. However, its effect on the eicosanoids and docosanoids that mediate the inflammatory response and inflammation resolution are unclear. We aimed to assess the effect of a single dose of intra-operative dexamethasone on peri-operative eicosanoids involved in inflammation including leukotriene B-4 (LTB4) and 20-hydroxyeicosatetraenoic acid (20-HETE), and inflammation resolution (Specialised Proresolving Mediators (SPM)).Patients and Methods: A subgroup of 80 patients from the randomised controlled PADDAG trial was enrolled into this substudy. They were allocated to receive 0, 4 or 8 mg dexamethasone administered intravenously at induction of anesthesia. Blood samples were collected before and 24 h after dexamethasone, for measurement of leukocytes, hs-CRP, LTB4, 20-HETE, the SPM pathway intermediates (14-HDHA, 18-HEPE and 17-HDHA) and SPMs (E-series resolvins, and D-series resolvins).Results: Compared to the administration of placebo, neutrophil count was elevated (P<0.05) 24 h after administration of 4 and 8 mg dexamethasone. Dexamethasone (8 mg) resulted in increased levels of LTB4 (P = 0.012) and 20-HETE (P = 0.009) and reduced hs-CRP levels (P<0.001). Dexamethasone did not significantly affect plasma SPM pathway intermediates or RvE3.Conclusion: Antiemetic doses of dexamethasone given during surgery increased plasma LTB4 and 20-HETE at a time when hs-CRP was significantly reduced. Plasma SPM pathway intermediates and RvE3 were unaffected.