The effects of resuscitation with different plasma products on endothelial permeability and organ injury in a rat pneumosepsis model

Abstract

Abstract Background Endothelial injury and permeability are a hallmark of sepsis. Initial resuscitation of septic patients with crystalloids is associated with aggravation of endothelial permeability, which may be related either to low protein content or to volume. We investigated whether initial resuscitation with different types of plasma or albumin decreases endothelial dysfunction and organ injury in a pneumosepsis rat model compared to the same volume of crystalloids. Study design and methods Sprague–Dawley rats were intratracheally inoculated with Streptococcus pneumoniae. Twenty-four hours after inoculation, animals were randomized to 2 control groups and 5 intervention groups (n = 11 per group) to receive resuscitation with a fixed volume (8 mL/kg for 1 h) of either Ringer’s Lactate, 5% human albumin, fresh frozen plasma derived from syngeneic donor rats (rFFP), human-derived plasma (hFFP) or human-derived solvent detergent plasma (SDP). Controls were non-resuscitated (n = 11) and healthy animals. Animals were sacrificed 5 h after start of resuscitation (T = 5). Pulmonary FITC-dextran leakage as a reflection of endothelial permeability was used as the primary outcome. Results Inoculation with S. Pneumoniae resulted in sepsis, increased median lactate levels (1.6–2.8 mM, p < 0.01), pulmonary FITC-dextran leakage (52–134 µg mL−1, p < 0.05) and lung injury scores (0.7–6.9, p < 0.001) compared to healthy controls. Compared to animals receiving no resuscitation, animals resuscitated with rFFP had reduced pulmonary FITC leakage (134 vs 58 µg/mL, p = 0.011). However, there were no differences in any other markers of organ or endothelial injury. Resuscitation using different human plasma products or 5% albumin showed no differences in any outcome. Conclusions Resuscitation with plasma did not reduce endothelial and organ injury when compared to an equal resuscitation volume of crystalloids. Rat-derived FFP may decrease pulmonary leakage induced by shock.

Keywords

• Albumin
• Endothelial dysfunction
• Plasma
• Resuscitation
• Sepsis
• Shock