Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs

Abstract

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS), colloids (Hextend [HEX]), and fresh frozen plasma (FFP) resuscitation are associated with differential effects on coagulation and endothelial systems. We subjected 15 Yorkshire swine to TBI and HS (40% blood volume), and kept in HS for 2hours before resuscitation with NS, HEX, or FFP. Markers of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1+2), and natural anticoagulation (activated protein C [aPC]) were determined in serum and brain whole cell lysates. Serum levels of aPC were greater in the NS group (203±30 pg/mL) compared with HEX (77±28 pg/mL; P=.02) and FFP (110±28 pg/mL; P=.09), as was PF 1 + 2 in the brain when compared with FFP (PF 1 + 2, 89±46 vs 37±14ng/mL; P=.035). Brain E-selectin was greater in the NS group compared with FFP (3.36±0.02 vs 3.31±0.01ng/mL; P=.029). Circulating ICAM-1 levels were increased in the NS group (151±9ng/mL) compared with the HEX (100±9ng/mL; P<.01) and FFP (108±9ng/mL; P=.01). In this clinically realistic large animal model of TBI+HS, NS resuscitation was associated with an early activation of coagulation, natural anticoagulation, and endothelial systems, compared with HEX and FFP.