Resuscitation with a hemoglobin-based oxygen carrier after severe brain trauma

Abstract

Introduction: Traumatic brain injury (TBI) is excluded from every clinical trial involving hemoglobin-based oxygen carriers (HBOCs). Furthermore, HBOCs are vasoactive, and pressor use in hemorrhagic shock is generally contraindicated. The purpose of this investigation was to examine low volume resuscitation with a vasoactive HBOC [hemoglobin glutamer-200 (bovine), BioPure Inc., Cambridge, MA] after TBI and hemorrhage. Methods: Anesthetized swine received TBI and hemorrhage (30 +/− 2ml/kg, n = 15). From 30 to 60 min, unlimited lactated Ringer’s (LR, n = 5), unlimited HBOC (n = 5), or 10ml/kg LR+unlimited HBOC (n = 5) was titrated to systolic blood pressure ≥ 100 mmHg. From 60 to 90 min, fluid was titrated to mean arterial pressure (MAP) > 70mmHg and blood (10ml/kg) was transfused for hemoglobin (Hb) 20 mmHg, LR if cerebral perfusion pressure (CPP) < 70mmHg, and blood if Hb < 5g/dL. Results: LR+HBOC reduced fluid requirements (30 +/− 12ml/kg vs 280 +/− 40 with LR+mannitol+blood, p < 0.05) and eliminated blood transfusions and mannitol. LR+HBOC attenuated ICP (12 +/− 1 vs 33 +/− 6mmHg with LR+mannitol+blood), and improved brain tissue pO2 (34.2 +/− 3.6 vs 16.1 +/− 1.6mmHg), cerebrovascular reactivity, and intracranial compliance (all p < 0.05). With HBOC and LR+HBOC, MAP and HR rapidly corrected, however with HBOC alone lactate failed to clear and systemic O2 extraction increased. Conclusions: 1. HBOC with initial crystalloid bolus was superior to LR+mannitol+blood following TBI. This may represent a new indication for HBOCs. 2. HBOC eliminated blood transfusions. 3. Vasoactive HBOCs, when used alone, can cause under-resuscitation despite restoration of MAP and HR, suggesting that MAP and HR are inadequate resuscitation endponts with HBOC use.