Blood substitute resuscitation as a treatment modality for moderate hypovolemia

Abstract

Blood substitute resuscitation as a treatment modality for moderate hypovolemia (∼40% blood loss) in a canine model has been evaluated using Oxyglobin® (Biopure Hemoglobin Glutamer-200/Bovine; a hemoglobin-based oxygen-carrier) and Hespan® (6% hetastarch; a nonoxygen-carrier) as resuscitants. Autologous (shed) blood served as control. Nine dogs were studied-after splenectomy, each dog was hemorrhaged (32-36 mL/kg; MAP = ∼50 mmHg) and randomly assigned to the three resuscitation groups. Microvascular, systemic function and oxygenation characteristics were monitored and/or measured simultaneously in prehemorrhagic (baseline), posthemorrhagic and postresuscitation phases for correlation-real-time microvascular changes in the bulbar conjunctiva were noninvasively measured via computer-assisted intravital microscopy and systemic function and oxygenation changes were monitored and/or measured via instrumentation and devices incorporated into our bioengineering station in an operating room setting. Blood chemistry was also studied for relevant measurements. Prehemorrhagic microvascular characteristics were similar in all animals (venular diameter = 41 ± 12 μm, A:V ratio = ∼ 1:2, red-cell velocity = 0.5 ± 0.3 mm/s). All animals also showed similar prehemorrhagic systemic function and oxygenation measurements comparable to a previous study and were consistent with normal measurements in dogs. At the completion of hemorrhaging to achieve moderate hypovolemia (∼40% blood loss with MAP at ∼50mm Hg), all nine animals showed similar significant (P < 0.01) posthemorrhagic microvascular changes, including ∼ 17% decrease in diameter (34 ± 7 μm), A:V ratio = variable, and ∼80% increase in velocity (0.9 ± 0.5 mm/s). All animals also showed similar significant (P < 0.01) posthemorrhagic systemic function and oxygenation changes, with decreases in Hct, aHbtotal, MPAP, MAP, SAP, DAP, CO, SV1, CaO 2, and CvO2 and increases in HR and lactic acidosis. Shed blood (control) resuscitation restored posthemorrhagic microvascular changes close to prehemorrhagic values (diameter= 39 ± 6 μm, A:V ratio=∼ 1:2, velocity = 0.6 ± 0.4 mm/s). Oxyglobind® and Hespand® restored microvascular changes in similar manner close to prehemorrhagic values (Oxyglobin®: diameter=38 ± 3 μm, A:V ratio= ∼1:2, velocity= 0.6 ± 0.4 mm/s; Hespan®: diameter= 38 ± 7 μm, A:V ratio= ∼1:2, velocity = 0.5 ± 0.4 mm/s). After resuscitation, shed blood (control) restored all systemic function and oxygenation changes close to prehemorrhagic values. However, both Oxyglobind® and Hespand® resuscitation restored systemic function changes, but not oxygenation changes, to prehemorrhagic values. This was an interesting finding because of the different oxygen-carrying capability of Oxyglobin® (oxygen-carrying) and Hespan® (nonoxygen-carrying). The result suggests that either volume replenishment alone (and not oxygen-carrying capibility) is needed to treat moderate hypovolemia or oxygenation measurements obtained by standard methods (oximetry, blood chemistry) may not reflect tissue oxygenation levels.