Lyophilized plasma prevents endothelial leak and improves oxygenation following traumatic hemorrhage

Abstract

Lyophilized plasma (LP) reconstituted to 100% (1×LP) or 50% (2×LP) of its original volume is just as effective as fresh frozen plasma (FFP) in correcting hemodynamic instability and coagulopathy following traumatic hemorrhagic shock. Compared to transfusion with lactated Ringers (LR), FFP also prevents the endotheliopathy of trauma (EOT) following hemorrhagic shock by attenuating vascular endothelial leak, which prevents endothelial damage, edema and end organ injury. Whether LP acts similarly to FFP on the vascular endothelium in preventing EOT is not known. Therefore, we hypothesized that similar to FFP, 1×LP and 2×LP would minimize endothelial permeability and prevent pulmonary dysfunction following traumatic hemorrhage. To test this hypothesis, two experiments were performed. To test for endothelial permeability in vitro, human pulmonary endothelial cells (HPECs) suspended in growth media were treated with FFP, 1×LP or 2×LP. Increased trans‐endothelial membrane resistance (TEER) indicated decreased permeability and barrier function recovery. When HPECs were treated in 10% plasma, the rise in TEER from baseline was similar in cells treated with FFP (22%) and 2×LP (27%), and highest with 1×LP treatment (33%, p<0.05 vs FFP and 2×LP). However, when cells were treated with 2% plasma, the rise in TEER was highest in HPECs treated with 2×LP (29%), followed by FFP (22%), and 1×LP (15%). To test for pulmonary dysfunction in vivo, anesthetized female swine subjected to 30min of uncontrolled hemorrhage from Grade V liver injury were resuscitated with lactated Ringers (LR), FFP, 1×LP or 2×LP. Following conscious recovery, arterial blood gasses were measured 24hrs post‐injury. PaO2 and arterial O2 saturation were low in LR‐treated swine (n=1; PaO2:52mmHg, O2:87%), but improved with FFP (n=2, PaO2:77±1mmHg, O2:97±0%), 1xLP (n=2; PaO2:73±8mmHg, O2:97±1%) and 2×LP (n=2; PaO2:72±4mmHg, O2:96±1%). Only LR‐treated swine exhibited gross pulmonary vascular thrombosis. Take together, these data suggests that LP and FFP act similarly to prevent endothelial permeability and pulmonary dysfunction after injury. Further experiments are required to determine if LP performs as well as FFP to minimize EOT and organ damage following hemorrhagic shock.Support or Funding InformationThis work was funded by DOD US Army Grant W81XWH‐04‐1‐0114 (Schreiber)