The impact of transfusion kinetics on the inflammatory response following major injury

Abstract

BACKGROUND The innate immune response is activated by tissue injury and may quickly become dysregulated in the setting of major trauma. Cytokines are a key component of this response and function to activate and mobilize neutrophils, macrophages, and natural killer cells. The purpose of this study was to understand how the kinetics of blood-based resuscitation may impact the cytokine response. Specifically, we hypothesize that transfusion kinetics make a fundamental contribution to the inflammatory response, beyond the volume of transfusion and injury severity. METHODS The Pragmatic, Randomized Optimal Platelet and Plasma Ratio data set was used in this retrospective analysis. Transfusion kinetics were quantified by calculating the total critical administration threshold episodes in three time periods, 1 to 2 hours following injury, 3 to 4 hours, and 5 to 6 hours following injury. The longitudinal response of key cytokines over 72 hours was assessed with a multivariable linear growth model, using critical administration threshold status as a time-varying covariate. RESULTS A total of 522 patients were included in this analysis. Pro-inflammatory cytokines interleukin (IL)-6 (p = 0.0354) and IL-8 (p < 0.0001) were significantly increased. Anti-inflammatory cytokines IL-1ra (p = 0.0001) and IL-10 (p < 0.0001) were significantly increased. Chemokines interferon-γ-inducible protein 10 (p = 0.0433), monocyte chemoattractant protein-1 (p = 0.0064), and macrophage inflammatory protein 1β (p = 0.0003) were significantly increased, while regulated up activation, normal T-cell expressed and secreted chemokine (p = 0.0216) was significantly decreased. Growth factors showed no significant response. CONCLUSION The kinetics of packed red blood cell transfusion demonstrate a potential association with the expression of cytokines following injury, beyond the total transfusion requirement or the severity of injury. Because cytokines activate and mobilize neutrophils, macrophages, and natural killer cells, these alterations may have a profound effect on degree and coordination of the immune response. As the contribution of various components of major resuscitation to inflammatory activation is clarified, such as types of blood product, tempo of transfusion, and operative care, targets for intervention should become more apparent. LEVEL OF EVIDENCE Therapeutic/Care Management; Level III.