Choice of Whole Blood versus Lactated Ringer's Resuscitation Modifies the Relationship between Blood Pressure Target and Functional Outcome after Traumatic Brain Injury plus Hemorrhagic Shock in Mice

Civilian traumatic brain injury (TBI) guidelines recommend resuscitation of patients with hypotensive TBI with crystalloids. Increasing evidence, however, suggests that whole blood (WB) resuscitation may improve physiological and survival outcomes at lower resuscitation volumes, and potentially at a lower mean arterial blood pressure (MAP), than crystalloid after TBI and hemorrhagic shock (HS). The objective of this study was to assess whether WB resuscitation with two different MAP targets improved behavioral and histological outcomes compared with lactated Ringer's (LR) in a mouse model of TBI+HS. Anesthetized mice (n = 40) underwent controlled cortical impact (CCI) followed by HS (MAP = 25-27 mm Hg; 25 min) and were randomized to five groups for a 90 min resuscitation: LR with MAP target of 70 mm Hg (LR70), LR60, WB70, WB60, and monitored sham. Mice received a 20 mL/kg bolus of LR or autologous WB followed by LR boluses (10 mL/kg) every 5 min for MAP below target. Shed blood was reinfused after 90 min. Morris Water Maze testing was performed on days 14-20 post-injury. Mice were euthanized (21 d) to assess contusion and total brain volumes. Latency to find the hidden platform was greater versus sham for LR60 (p < 0.002) and WB70 (p < 0.007) but not LR70 or WB60. The WB resuscitation did not reduce contusion volume or brain tissue loss. The WB targeting a MAP of 60 mm Hg did not compromise function versus a 70 mm Hg target after CCI+HS, but further reduced fluid requirements (p < 0.03). Using LR, higher achieved MAP was associated with better behavioral performance (rho = -0.67, p = 0.028). Use of WB may allow lower MAP targets without compromising functional outcome, which could facilitate pre-hospital TBI resuscitation.