Oxygen Transport Dynamics after Resuscitation with a Conjugated Hemoglobin Solution

Hypothesis: Pyridoxalated hemoglobin polyoxyethylene conjugate (PHP), a hemoglobin-based oxygen carrier, is effective in restoring hemodynamic balance and oxygen delivery after moderate hemorrhage but may be less effective in off-loading oxygen at the tissue level. Design: Before-after trial. Setting: Animal research laboratory of an academic institution. Participants: Ten female Yorkshire swine. Interventions: Anesthetized swine underwent a 25% controlled hemorrhage followed by resuscitation with crystalloid plus either shed blood or PHP. Hemodynamic parameters, including heart rate, mean arterial pressure, mean pulmonary arterial pressure, and cardiac index were continuously monitored. Arterial and mixed venous blood samples were collected at baseline, after hemorrhage, after resuscitation, and every 15 minutes for 90 minutes after resuscitation. Oxygen delivery and consumption, oxygen extraction ratios, and percentage of contribution to oxygen delivery and consumption were determined in whole blood, red blood cells, and plasma by using a compartmentalized approach. Main Outcome Measures: Intergroup and intra-group comparisons were performed for hemodynamic parameters and oxygen transport dynamics. Results: Heart rate returned closer to baseline levels in the PHP group (P<.05) and mean pulmonary arterial pressure was transiently elevated after infusion of PHP (P=.028), but otherwise no significant differences in hemodynamic balance were observed. The extraction ratio from the red blood cells in the PHP group more than doubled, whereas the extraction ratio from plasma remained constant. The percentage of contribution of plasma, including PHP, to oxygen delivery exceeded 20% (P < .05), but the relative contribution to oxygen consumption did not markedly change from baseline. Conclusions: Pyridoxalated hemoglobin polyoxyethylene conjugate is at least as effective as shed blood in restoring hemodynamic balance and oxygen delivery after moderate hemorrhage. There is a disproportionately low contribution from plasma to oxygen consumption, which suggests that PHP may act as an oxygen sink in moderate anemia.