The effects of balanced crystalloid versus plasma on endothelial injury, systemic inflammation, and coagulation in experimental endotoxaemia: a randomised human volunteer study.

Abstract

During shock, neutrophil-mediated glycocalyx degradation can lead to exposure of the procoagulant endothelial surface and consequent organ injury. Resuscitation using crystalloid fluids may augment this endothelial damage, while resuscitation using plasma may preserve glycocalyx health. We hypothesised that resuscitation with plasma would preserve glycocalyx integrity by reducing inflammation, glycocalyx shedding, and dyscoagulation in a controlled model of systemic inflammation in human volunteers. Twelve healthy male volunteers were injected with 2 ng kg^-1 lipopolysaccharide (LPS) to induce systemic inflammation. Thirty minutes after LPS administration, participants were randomised to receive 10 ml kg^-1 of either balanced salt solution or solvent detergent plasma (SDP). Plasma syndecan-1, a marker of glycocalyx degradation, was the primary outcome. Additionally, plasma biomarkers of inflammation, neutrophil extracellular trap formation, glycocalyx degradation, endothelial injury, and coagulation were measured serially, by bead-based or enzyme-linked immunoassays. LPS induced a systemic inflammatory response, accompanied by endothelial injury as indicated by increased levels of syndecan-1 (median increase: 2920-4430 pg ml^-1, P<0.05). Participants receiving SDP had lower levels of neutrophils and plasma matrix metalloproteinase-9, compared with those receiving balanced salt solution. Neutrophil extracellular trap formation, inflammation, and glycocalyx degradation were not affected by fluid therapy. SDP reduced LPS-induced prolonged prothrombin time, but had no impact on other biomarkers of coagulation. In human endotoxaemia, plasma resuscitation reduced leucocyte and neutrophil levels but did not reduce glycocalyx degradation, when compared with equal volume resuscitation with a balanced crystalloid solution.