The effect of plasma versus crystalloids on intravascular volume, tissue perfusion and tissue oxygenation: a randomized controlled trial in a human endotoxemia model

Fluid resuscitation is a cornerstone of shock treatment to ensure sufficient tissue perfusion. However, large volumes of crystalloids are associated with adverse outcomes and plasma has been suggested as an alternative fluid. This trial investigated the effect of plasma transfusion on circulation, tissue perfusion, and mitochondrial oxygen tension (mitoPO2) compared with balanced crystalloids in a human endotoxemia model. Twelve healthy volunteers were subjected to 2 ng/kg lipopolysaccharide (LPS) infusion. Six participants received 10 ml/kg of plasma. In the control group, 10 ml/kg of balanced crystalloids was infused. Non-invasive cardiac index (CI), markers of the microcirculation and mitoPO2 were measured at prespecified time points. Blood volume was estimated by hemoglobin levels at each timepoint. Differences in groups over time were tested using linear mixed modeling. Wilcoxon rank-sum test was used to test the statistical difference between groups at each timepoint. LPS infusion resulted in a systemic inflammatory reaction with an increase in temperature and leukocytes. Heart rate and CI increased, while systemic vascular resistance (SVRI) decreased. Capillary refill time, mitoPO2 and perfused sublingual vessels all deteriorated, indicative of hyperdynamic vasodilation with redistribution of blood volume. Plasma increased intravascular volume by 4 ml/kg one hour after infusion, whereas intravascular volume remained at baseline with crystalloids (p < 0.01). Subsequently, CI increased more in the plasma group compared to the crystalloid group (p < 0.05). Tissue perfusion was improved in the plasma group, with shorter capillary refill time (p < 0.05) and a higher proportion of perfused vessels compared to the crystalloid group (p < 0.05). After fluid infusion, mitoPO2 increased less in the plasma group compared to the crystalloid group (p < 0.05). In healthy endotoxemic volunteers without shock, plasma infusion augmented intravascular blood volume and cardiac output, resulting in improved microcirculatory tissue perfusion compared to crystalloids. However, plasma did not restore the reduction in skin mitoPO2 as much as crystalloids. EudraCT ID: EUCTR2020-005045-17-NL. Date of registration: 14-12-2021