Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function (EMPIRE)

Effect of Intravenous Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function in Patients With Colon Cancer

Ideally, the postoperative inflammatory response is part of a well-orchestrated mechanism that contributes to tissue healing and rapid recovery. An exaggerated uncontrolled inflammatory response, however may lead to catabolism, tissue damage and organ failure. Omega-3 fatty acids may provide a means to alter cellular immune responses to the benefit of the patient. When omega-3 fatty acids are incorporated into membranes of inflammatory cells, they trigger intracellular signalling pathways that result in a less pro-inflammatory response. They modify gene and protein expression, modulate membrane protein activity and act as a reservoir for bioactive molecules. They also have a strong anti-inflammatory effect by mediating resolution of the inflammation. Furthermore, omega-3 fatty acids improve erythrocyte function, which is vital for an adequate microcirculation, tissue oxygenation and wound healing. The investigators hypothesize that the perioperative administration of intravenous omega-3 fatty acids results in a rapid incorporation in immune cells and erythrocytes, thereby reducing the postoperative inflammatory response and improving erythrocyte function in patients undergoing colorectal surgery.

purified fish oil, omega-3 fatty acids, eicosapentaenoicacid (EPA), docosahexaenoicacid (DHA), dl-a- tocopherol (antioxidant), Omegaven-Fresenius

Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine IL-6, measured in ng/ml.

Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine TNF-α (tumor necrosis factor-α), and the anti-inflammatory cytokine IL-10 (interleukine-10), both measured in ng/ml.

Erythrocyte deformability and aggregation measured by LORRCA (laser assisted optical rotational red cell analyzer)

White blood cell count, C-reactive protein and cytokine levels (Interleukine-6, Tumor Necrosis Factor-α and Interleukine-10) in serum.

Length of hospital stay and occurence of surgical site infection, abscess, urinary tract infection, pneumonia, anastomotic leakage, need for Intensive Care Unit admission, Systemic Inflammatory Response Syndrome, Multi Organ Failure, any adverse events.

Neuropsychological examination using a reading test, an auditory verbal learning test, WAIS III figure series and trail making tests.

Inclusion Criteria: Patients (male or female) undergoing elective laparoscopic surgery for colon cancer Age between 60 and 80 years BMI between 20 kg/m2 and below 30 kg/m2 Written informed consent Exclusion Criteria: Participation in or having participated in another clinical trial within the previous 3 months Indications for continuously use of anticoagulant medication and no possibility to stop these medication perioperatively, for example patients with an artificial heart valve Pre-operative Hemoglobin<5.0 mmol/L Metastatic disease Very poor peripheral venous access Current history of inflammatory or infectious disease The use of anti-inflammatory drugs The use of thyroid medication The use of fish oil products or fish consumption more than 2 times a week Contra-indication for the use of Omegaven-Fresenius, including: General contra-indications for parenteral nutrition Allergy to fish or egg protein.

Bakker N, van den Helder RS, Stoutjesdijk E, van Pelt J, Houdijk APJ. Effects of perioperative intravenous omega-3 fatty acids in colon cancer patients: a randomized, double-blind, placebo-controlled clinical trial. Am J Clin Nutr. 2020 Feb 1;111(2):385-395. doi: 10.1093/ajcn/nqz281.