Inadequacy of low-volume resuscitation with hemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) in canine hypovolemia

Stroma-free hemoglobin-based oxygen carriers (HBOC) have been developed to overcome problems associated with transfusion of allogeneic blood. We have studied the efficacy of the first licensed veterinary blood substitute, hem oglobin glutamer-200 bovine (Oxyglobin(R); Biopure, Cambridge, MA, USA, Hb- 200), in a canine model of acute hypovolemia and examined whether clinicall y commonly used criteria are adequate to guide fluid resuscitation with thi s product. Twelve anesthetized dogs were instrumented for measurements of p hysiological variables including hemodynamic, oxygenation, and blood gas an d acid-base parameters. Dogs were bled to a mean arterial pressure (MAP) of 50 mmHg for 1 h followed by resuscitation with either shed blood (controls ) or Hb-200 until heart rate (HR), MAP and central venous pressure (CVP) re turned to baseline. Recordings were repeated immediately and 3 h after term ination of fluid resuscitation. Hemorrhage (average 32 mL/kg) caused signif icant decreases in total hemoglobin (Hb), mean pulmonary arterial pressure (PAP), cardiac output (CO) and oxygen delivery (DO2I), increases in HR and systemic vascular resistance (SVRI), and lactic acidosis. In controls, only re-transfusion of an shed blood returned HR, MAP and CVP to prehemorrhage values, whereas in other dogs this endpoint was reached with infusion of 10 mL/kg Hb-200. Unlike blood transfusion, Hb-200 infusion failed to return C I and DO2I to baseline and to increase arterial oxygen content (CaO2) and t otal Hb; SVRI further increased. Thus, commonly used criteria (HR, MAP, CVP ) to guide transfusion therapy in patients posthemorrhage prove insufficien t when HBOCs with pronounced vasoconstrictive action are used and lead to i nadequate volume repletion.