Resuscitation From Traumatic Brain Injury (TBI) and Secondary Hypotension With a Hemoglobin-Based Oxygen Carrying Solution (HBOC)

Introduction: We have observed that early transfusion with shed blood vs saline improved cerebral perfusion pressure (CPP) and cerebral venous outflow saturation (CvO2) when hypotension was superimposed on TBI. In patients, it may be difficult to transfuse within the golden hour , which has led to searches for blood substitutes. HBOCs have shown promise in many different models, and are now in phase III clinical trials. However, the potential benefits may be outweighed by vasoconstriction due to NO scavenging. Methods: Anesthetized, ventilated swine (37±1kg) received a fluid-percussion injury and 30% hemorrhage. After 1 hr, resuscitation consisted of 500ml of Baxter\u27s first generation HBOC (DCLHb, n=6) or saline (SAL, n=5), followed by supplemental fluid. To test cerebral vasoreactivity, FiCO 2 = 0.05 and hyperventilation were administered for 10 minutes pre- and post-resuscitation. At 72 hrs, the brains were removed for histopathology. Results: CPP (table) and arterial lactate were significantly higher following DCLHb vs. SAL resuscitation (lactate: 3.3±0.5 vs 1.2±0.2, p\u3c0.05). CvO2changes to the CO2 challenge were similar (table). Histologic findings included subarachnoid hemorrhage, diffuse axonal injury, and infarcts. DCLHb did not aggravate these changes. Conclusions: 1) Initial resuscitation with DCLHb improved CPP but increased systemic lactate, both manifestations of systemic vasoconstriction; 2) Since there was no harmful physiologic or histologic cerebral sequela related to vasoconstriction with this first generation HBOC, second generation compounds with less NO scavenging properties may have therapeutic potential for resuscitation of TBI. CPP @ 30 min Hi CO2 - Δ CvO2 sat Lo CO2 - Δ CvO2 pre TBI post TBI pre TBI DCLHb 78±5 -4±4 -11±4 21±3 Saline 56±3 -4±2 -10±3 22±2