Hemoglobin-Based Oxygen Carriers: Development and Clinical Potential

Ketcham, Eric; Cairns, Charles B.

doi:10.1016/s0196-0644(99)70370-7

Cited by 43 publications

(24 citation statements)

References 67 publications

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“…First and most importantly, HBOC-201 does not require refrigeration and has a shelf life of two years at room temperature, characteristics crucial to out-of-hospital and military environments. 13 In its polymerized form, HBOC-201 has a P 50 of 38 mm Hg (human red cells, P 50 26.5 mm Hg), which lowers its affinity for oxygen, thereby favoring its release in tissue. HBOC-201 has an osmolarity of 300 mOsm/kg and a colloid osmotic pressure similar to human plasma (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…12 One hemoglobin solution, HBOC-201, has properties similar to human plasma with oxygen-dissociation characteristics that favor oxygen delivery in tissue (Table 1). 13 In contrast to banked blood, HBOC-201 can be used without cross-matching or viral testing and is stable at room temperature for up to two years. While research with HBOC-201 has demonstrated potential increases in vasoconstriction, reflected by decreases in cardiac output when used in various models, 14,15 to the best of our knowledge, no research study has been performed with HBOC-201 resuscitation while directly monitoring vital organ oxygenation.…”

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confidence: 99%

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Small-volume Resuscitation with HBOC-201: Effects on Cardiovascular Parameters and Brain Tissue Oxygen Tension in an Out-of-hospital Model of Hemorrhage in Swine

et al. 2002

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Objective: Hemoglobin-based oxygen carriers, such as HBOC-201, offer several potential advantages over conventional resuscitation solutions or banked blood in the acute treatment of hemorrhagic shock. While previous studies with some hemoglobin solutions revealed vasoactive effects resulting in decreased oxygen delivery, these investigations were performed without directly measuring vital tissue oxygenation. The authors tested the hypothesis that a small-volume bolus of HBOC-201 would improve and sustain brain tissue oxygen tension (PbrO 2 ) without adverse effects on cardiovascular endpoints, when used in an acute out-of-hospital hemorrhage model. Methods: Male Yorkshire swine (n = 7) were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg while monitoring standard hemodynamic parameters. In addition, Clark-type polarographic probes were directly inserted into brain tissue to measure PbrO 2 . Following institution of high-flow oxygen (FiO 2 = 1.0), resuscitation was performed with a bolus infusion of HBOC-201 (6 mL/kg). Swine were observed for two hours. Results: Cardiac output (CO), MAP, pulmonary artery diastolic pressure (PAD), and PbrO 2 all decreased significantly with hemorrhage (p < 0.05). Immediately following resuscitation with HBOC-201 (mean volume = 239 mL), MAP and CO were restored to 83% and 84% of baseline levels, respectively. PbrO 2 increased significantly after treatment with HBOC-201, surpassing baseline levels by 66%. PAD rose above baseline levels during observation, but this increase was not significantly different from baseline levels (24.0 mm Ϯ 4.1 vs. 22.7 mm Ϯ 7.4). Conclusions: Small-volume resuscitation with HBOC-201 rapidly restored hemodynamic parameters and PbrO 2 following severe hemorrhage without detrimental vasoactive effects and without compromise to directly monitored brain tissue oxygenation. The results of this preliminary study demonstrate that HBOC-201 could potentially improve current resuscitation measures and that further investigations with HBOC-201 are warranted.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Small-volume Resuscitation with HBOC-201: Effects on Cardiovascular Parameters and Brain Tissue Oxygen Tension in an Out-of-hospital Model of Hemorrhage in Swine

et al. 2002

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“…105,106 These effects are thought to be due to the scavenging of NO by SFH. 106 Nitric oxide can combine with hemoglobin either at the heme site to form methemoglobin or at the protein site to form S-nitrosohemoglobin.…”

Section: Hemoglobin-based Blood Substitutesmentioning

confidence: 99%

Bench to Bedside Nitric Oxide in Emergency Medicine

Lopez

Christopher

Griswold³

et al. 2000

Academic Emergency Medicine

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“…An alternative to this RBC transfusion might be the immediate infusion of a hemoglobin-based artificial oxygen carrier (HBOC) [7,8]. HOBCs are hyperoncotic solutions acting like 'plasma expanders' with the ability to transport O 2 [9]. Therefore, most of the HBOCs seem to be suitable for the initial treatment of hemorrhagic shock.…”

Section: Introductionmentioning

confidence: 99%

Diaspirin Cross-Linked Hemoglobin Fails to Improve Left Ventricular Diastolic Function after Fluid Resuscitation from Hemorrhagic Shock

et al. 2001

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In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O₂ content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dt_min) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (τ) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock.

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Hemoglobin-Based Oxygen Carriers: Development and Clinical Potential

Cited by 43 publications

References 67 publications

Small-volume Resuscitation with HBOC-201: Effects on Cardiovascular Parameters and Brain Tissue Oxygen Tension in an Out-of-hospital Model of Hemorrhage in Swine

Small-volume Resuscitation with HBOC-201: Effects on Cardiovascular Parameters and Brain Tissue Oxygen Tension in an Out-of-hospital Model of Hemorrhage in Swine

Bench to Bedside Nitric Oxide in Emergency Medicine

Diaspirin Cross-Linked Hemoglobin Fails to Improve Left Ventricular Diastolic Function after Fluid Resuscitation from Hemorrhagic Shock

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