Prolonged Low-Volume Resuscitation with HBOC-201 in a Large-Animal Survival Model of Controlled Hemorrhage

Fitzpatrick, Colleen; Biggs, Kristen L.; Atkins, B. Zane; Quance-Fitch, Fonzie; Dixon, Patricia; Savage, Stephanie A.; Jenkins, Donald H.; Kerby, Jeffrey D.

doi:10.1097/01.ta.0000174730.62338.88

Cited by 20 publications

(7 citation statements)

References 9 publications

(8 reference statements)

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“…Our experimental model was developed to obtain a total volume exchange that mimicked previously published articles wherein hemorrhage or isovolemic hemodilution was carried out to remove 50% of the animals total blood volume or attain a cumulative 50% volume exchange. 4–6, 9–11 These earlier studies suggested that this “stress” would result in the development of a metabolic acidosis (lactic acidosis) presumably from inadequate oxygen delivery or maldistribution of blood flow and low tissue oxygen tension. A recent study, using an experimental design similar to the current study, however, suggested that physiologic coupling of oxygen delivery and consumption after administration of HBOC-201 is not impaired.…”

Section: Discussionmentioning

confidence: 99%

Vital Organ Tissue Oxygenation After Serial Normovolemic Exchange Transfusion with HBOC-201 in Anesthetized Swine

Muir¹,

Ilangovan²,

Zweíer³

et al. 2011

Shock

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This study determined the effects of serial, normovolemic, stepwise exchange transfusions with either 6% human serum albumin (HSA) or the hemoglobin-based oxygen carrier, HBOC-201, on tissue oxygenation of the heart, brain and kidney in intact anaesthetized pigs. Exchange transfusions to 10%, 30% and 50% of the pigs total blood volume were completed at a withdrawal rate of 1.0 ml/kg/min followed by an infusion rate of 0.5 ml/kg/min of HBOC-201 or iso-oncotically matched 6% HSA. Measurements included invasive systemic hemodynamic (blood pressures, left ventricular end diastolic pressure [LVEDP]), hematolic (hemoglobin, hematocrit, methemoglobin), acid-base (pH, pCO2) and biochemistry (serum lactate) measurements. Brain and kidney tissue oxygenation (tPO2) were determined by electron paramagnetic resonance (EPR) and heart tPO2 by O2 sensitive fiber optic probe. The main results demonstrated that tPO2 after HBOC-201 remained stable despite significant decreases in hematocrit and changing hemodynamics. In vivo tPO2 measurements (heart tPO2 average ≥ 22 mm Hg; brain tPO2 average ≥ 8 mmHg; and kidney tPO2 average ≥10 mmHg) were maintained in all groups at all times. Blood pressures were 20–30 mm Hg higher after HBOC-201 compared to HSA controls. Heart rate and LVEDP were not different among treatment groups. In conclusion, the administration of HBOC-201 maintained tPO2 in three vital organs after profound hemodilution.

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Section: Discussionmentioning

confidence: 99%

Vital Organ Tissue Oxygenation After Serial Normovolemic Exchange Transfusion with HBOC-201 in Anesthetized Swine

Muir¹,

Ilangovan²,

Zweíer³

et al. 2011

Shock

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“…Interestingly, in at least one study using a swine model of hemorrhagic shock, clinical outcome was improved, but the improved outcome was associated with evidence of clinically relevant adverse histologic changes in several organs, including heart, lung, liver, and kidney (32). However, it would be unfair to imply that HBOC infusion is always associated with reduced cardiac output or does not improve survival in a variety of hemorrhagic and other models of trauma, as there are many examples of investigations supporting the use of HBOC infusion in models of trauma (11, 28, 29, 33–35). According to this study, it would be important to know the hemodynamic, clinical outcome, and tissue histologic effects of the combination of PDE5 inhibition with HBOC used for low volume/low pressure resuscitation.…”

Section: Discussionmentioning

confidence: 99%

Glutaraldehyde-polymerized bovine hemoglobin and phosphodiesterase-5 inhibition*

Gotshall

Hamilton

Foreman

et al. 2009

Critical Care Medicine

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Objective Hemoglobin-based oxygen carriers (HBOC) of several types scavenge nitric oxide from the vasculature resulting in vasoconstriction and hypertension, both systemic and pulmonary. Phosphodiesterase-5 (PDE5) inhibitors promote nitric oxide activity and enhance vasodilation. The purpose of this study was to determine whether combined therapy of glutaraldehyde-polymerized bovine hemoglobin (HBOC) with a PDE5 inhibitor would counter the negative hemodynamic consequences of HBOC therapy alone, resulting in improved hemodynamics and oxygen delivery. Design A controlled, experimental study. Setting A research laboratory at a university. Subjects Conscious male Sprague-Dawley rats. Interventions Glutaraldehyde-polymerized bovine hemoglobin (HBOC), sildenafil (PDE5 inhibitor), and lactated Ringer’s solution (control). Measurements and Main Results Infusion of the HBOC resulted in significant (p < 0.05) systemic and pulmonary vasoconstriction, with reduced cardiac output and reduced oxygen delivery to the periphery. Infusion of lactated Ringer’s demonstrated no changes in the measured variables. Infusion of sildenafil alone reduced systemic and pulmonary artery blood pressure, while maintaining cardiac output and oxygen delivery. Combined HBOC and sildenafil infusion resulted in stable systemic blood pressure, cardiac output, and oxygen delivery. However, the addition of sildenafil to HBOC did not fully ameliorate the pulmonary vasoconstriction caused by HBOC. Conclusion The HBOC used in this study resulted in pulmonary and systemic hypertension, reduced cardiac output, and oxygen delivery. These negative consequences of HBOC treatment can be largely overcome by combing HBOC treatment with a PDE5 inhibitor (sildenafil). Thus, these data support the continued investigation of combined HBOC and PDE5 inhibitor treatment in circumstances in which HBOC therapy is being considered.

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“…In these surviving NON animals, the laboratory indices may initially remain “artificially” closer to baseline levels due to the absence of fluid‐induced hemodilution effects; however, physiologic and hemostatic effects might have been observed in a longer survival model. Fitzpatrick and coworkers 33 reported equivalent 5‐day survival with no evidence of organ dysfunction in swine resuscitated with HBOC‐201 or HEX 33 . Therefore, extending survival time (i.e., >7 days) might provide better evidence for long‐term benefits of HBOC‐201.…”

Section: Discussionmentioning

confidence: 99%

Hematology patterns after hemoglobin‐based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care

et al. 2007

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In this severe model, survival was equivalent with HBOC-201 and HEX resuscitation. HBOC-201 or HEX allowed delayed hospital arrival to 24 hours without worsening coagulation parameters, but dilutional mild coagulopathy in the hospital phase persisted with HBOC-201 due to blood transfusion avoidance. Low hematocrit suggests that blood administration after HBOC-201 resuscitation could be beneficial to replete blood cellular mass.

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Prolonged Low-Volume Resuscitation with HBOC-201 in a Large-Animal Survival Model of Controlled Hemorrhage

Abstract: HBOC-201 more effectively restored and maintained perfusion pressures with lower volumes, and allowed for improved survival. These data suggest that hemoglobin-based oxygen carriers are superior to the current standard of care for resuscitation in far-forward military operations.

Cited by 20 publications

References 9 publications

Vital Organ Tissue Oxygenation After Serial Normovolemic Exchange Transfusion with HBOC-201 in Anesthetized Swine

Vital Organ Tissue Oxygenation After Serial Normovolemic Exchange Transfusion with HBOC-201 in Anesthetized Swine

Glutaraldehyde-polymerized bovine hemoglobin and phosphodiesterase-5 inhibition*

Hematology patterns after hemoglobin‐based oxygen carrier resuscitation from severe controlled hemorrhage with prolonged delayed definitive care

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