Abstract
Hemoglobin-based oxygen carriers (HBOCs) are solutions of cell-free hemoglobin (Hb) that have been developed for replacement or augmentation of blood transfusion. It is important to monitor in vivo tissue hemoglobin content, total tissue hemoglobin [THb], oxy- and deoxy-hemoglobin concentrations ([OHb], [RHb]), and tissue oxygen saturation (S(t)O(2)=[OHb][THb]x100%) to evaluate effectiveness of HBOC transfusion. We designed and constructed a broadband diffuse optical spectroscopy (DOS) prototype system to measure bulk tissue absorption and scattering spectra between 650 and 1000 nm capable of accurately determining these tissue hemoglobin component concentrations in vivo. Our purpose was to assess the feasibility of using DOS to optically monitor tissue [OHb], [RHb], S(t)O(2), and total tissue hemoglobin concentration ([THb]=[OHb]+[RHb]) during HBOC infusion using a rabbit hypovolemic shock model. The DOS prototype probe was placed on the shaved inner thigh muscle of the hind leg to assess concentrations of [OHb], [RHb], [THb], as well as S(t)O(2). Hemorrhagic shock was induced in intubated New Zealand white rabbits (N=6) by withdrawing blood via a femoral arterial line to 20% blood loss (10-15 cckg). Hemoglobin glutamer-200 (Hb-200) 1:1 volume resuscitation was administered following the hemorrhage. These values were compared against traditional invasive measurements, serum hemoglobin concentration (sHGB), systemic blood pressure, heart rate, and blood gases. DOS revealed increases of [THb], [OHb], and tissue hemoglobin oxygen saturation after Hb-200 infusion, while blood total hemoglobin values continued did not increase; we speculate, due to hyperosmolality induced hemodilution. DOS enables noninvasive in vivo monitoring of tissue hemoglobin and oxygenation parameters during shock and volume expansion with HBOC and potentially enables the assessment of efficacy of resuscitation efforts using artificial blood substitutes.
Highlights
Hemorrhage remains a leading cause of death in civilian and military trauma patients, and a major cause of morbidity and mortality in patients with medical illnesses, vascular events, and patients undergoing surgery
As in previous studies, we have demonstrated the ability of noninvasive diffuse optical spectroscopy (DOS) to detect changes in tissue perfusion resulting from reduction in blood volume induced by progressive hemorrhage.[15,26,27]
There are a number of limitations of the current study, these promising initial findings suggest that noninvasive DOS measurements may be very useful for detection and optimization of the effects of blood substitute resuscitation on peripheral perfusion
Summary
Hemorrhage remains a leading cause of death in civilian and military trauma patients, and a major cause of morbidity and mortality in patients with medical illnesses, vascular events, and patients undergoing surgery. Limitations, availability, costs, infection risks, logistical issues, and complications of blood transfusions for resuscitation of hemorrhage have led to extensive efforts to develop safe and effective blood substitutes.[1] A number of blood substitute approaches have been pursued, including development of an approved commercially available polymerized hemoglobin-based veterinary blood oxygen carrier (HBOC) product, hemoglobin glutamer-200 (Hb-200, Oxyglobin®, Biopure Corporation, Cambridge, Massachusetts).[1,2,3,4,5,6,7,8,9,10,11,12,13,14]. Standard methods for assessment of adequacy of resuscitation during hemorrhage, including hematocrit, serum hemoglobin concentration, cardiac output, blood pressure, and pulse rate, are insensitive and nonspecific due to dynamic physiologic and reflex responses of the hemorrhaging patient.[16,17,18,19] These difficulties in assessing adequacy of hemorrhage resuscitation are further compounded during blood substitute resuscitation due to interaction of complex factors, including differences between blood and cell-free blood substitutes.[1,10,13] Some of the factors that may differentially affect tissue perfusion and oxygenation during hemoglobin-based blood substitute treatment include polymerized heme structures, heterogeneous polymer size distribution, NO scavenging, gas transfer from cell stromal free composition, and osmolality effects.[1,6,12,13,20,21]
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