Neutrophil phenotypes quantify tissue damage caused by major surgery

Emma Josephine de Fraiture ^1* Ted Reniers ² Nathalie EW Vreeman ² Thijs CD Rettig ³ Hjalmar C Van Santvoort ² Angela Bikker ² Nienke Vrisekoop ¹ Leo Koenderman ¹ Falco Hietbrink ¹ Peter G Noordzij ²

• ¹ University Medical Center Utrecht, Utrecht, Netherlands
• ² St. Antonius Hospital, Nieuwegein, Netherlands
• ³ Amphia Ziekenhuis, Breda, Netherlands

Introduction: Major surgery triggers an innate immune response, that can become excessive, leading to immune suppression and increased infection risk. Neutrophils are crucial in this response, and changes in their phenotype are associated with the severity of the innate immune response. This study examines the effect of major surgery on neutrophil phenotypes using fast automated flow cytometry.In this prospective single-center cohort study, adult patients undergoing either pancreaticoduodenectomy or on-pump coronary artery bypass grafting (CABG) were enrolled as part of the (BIGPROMISE) study. Blood samples were collected preoperatively (after anesthesia induction) and postoperatively (immediately after surgery). Neutrophil phenotypes were assessed by automated 24/7 flow cytometry with a fast analysis time of less than 30 minutes.The study included 24 CABG patients and 12 pancreaticoduodenectomy patients.Preoperative neutrophil heterogeneity was minimal, but significant postoperative changes in neutrophil subsets were observed in all patients, indicating acute systemic inflammation. Patients who underwent pancreatic surgery showed a more extensive inflammatory response, with 83% in category 5, compared to 29% in the CABG group.Conclusions: This is the first study to use fully automated flow cytometry to monitor perioperative changes in neutrophil phenotypes following major surgery. Our findings provide a more in-depth readout of the innate immune response and neutrophil activation, highlighting a more pronounced response to pancreatic surgery compared to cardiac surgery. Neutrophil phenotyping could serve as a valuable biomarker for patient stratification and management, though larger cohort studies are needed to confirm its predictive value for postoperative complications.