Fatty Acid-Saturated Albumin Reduces High Mortality and Fluid Requirements In A Rat Model of Hemorrhagic Shock Plus Tourniquet and Hypotensive Resuscitation.

Military pre-hospital care for hemorrhage is often characterized by use of tourniquets (TQ) and permissive hypotensive resuscitation (PHR) with crystalloids or colloids, but these treatments have not been previously combined in an animal model. Although albumin resuscitation solutions have been tested, the potential effects of non-esterified fatty acids (NEFAs) bound to albumin have not been evaluated in vivo, and few studies have investigated concentrated albumin solutions to reduce fluid requirements. We created a militarily relevant rat model of trauma and hemorrhagic shock (T/HS) (27 ml/kg hemorrhage) with TQ and PHR. We investigated the ability of resuscitation with concentrated (250 mg/ml) albumin, followed by Plasmalyte as needed to maintain PHR, to reduce fluid volumes (vs. Plasmalyte alone, N = 17). Albumin was free of non-esterified fatty acids (N = 15) or saturated with oleic acid (OA; N = 13). The model resulted in high (53%) mortality within 3 hours of injury. Only OA-saturated albumin was able to significantly reduce mortality (from 47% to 8%) and fluid requirements (from 56 to 6 ml/kg) compared to Plasmalyte alone. Plasma NEFA-binding capacity was saturated earliest in the OA-saturated albumin group. Likewise, OA-saturated albumin tended to increase cell-free hemoglobin in the broncheoalveolar lavage fluid, which was significantly associated with survival. Our findings suggest incorporating TQ and PHR in T/HS models may result in high mortality and fluid requirements and that OA-saturated albumin, but not NEFA-free albumin or Plasmalyte alone, may provide a benefit to early survival and resuscitation volume, though a hemolytic mechanism may have later consequences, so caution is advised.