Measuring Circulating Blood Volume Using Infused Hemoglobin-Based Oxygen Carrier (Oxyglobin®) as an Indicator: Verification in a Canine Hypovolemia Model

Abstract

Direct determination of the circulating blood volume (CBV) is clinically desirable, especially when hemodynamic parameters such as blood pressure and heart rate are pharmacologically altered and may not be used with confidence for monitoring of CBV. In a rabbit model, we demonstrated that small volumes of hemoglobin-based oxygen carriers (HBOC) may be used for measuring of CBV with the indicator-dilution technique. This study aimed to verify the technique in a canine hypovolemia model with varying concentrations of infused HBOC. Twenty-four healthy mongrel dogs were anesthetized and anesthesia maintained with isoflurane in 21% oxygen and sufentanil infusion. All animals were mechanically ventilated. After splenectomy and insertion of arterial, venous, and balloon-tipped pulmonary arterial catheters and recording of baseline values of total and plasma hemoglobin (Hb), hematocrit, and major hemodynamic parameters, dogs were bled (average 36.6 +/- 5.8 mL/kg) to a mean arterial pressure of 50 mm Hg and maintained hypovolemic for 1 hour. Thereafter, measurements were repeated, and dogs were resuscitated. Animals in group 1 were resuscitated with 30 mL/kg of 6% hetastarch solution (HES). Animals in other groups received either 10 mL/kg of Hb glutamer-200 (Hb-200; Oxyglobin) plus 20 mL/kg HES (group 2), 20 mL/kg Hb-200 plus 10 mL/kg HES (group 3), or 30 mL/kg Hb-200 (group 4). Solutions were infused at 30 mL/kg/hr. Measurements were repeated immediately after volume resuscitation. Plasma Hb concentration was determined after centrifugation using the HemoCue. Lactated Ringer's solution was infused in all subjects at 5 mL/kg/hr for maintenance. CBV at baseline was estimated as 85 mL/kg. CBV values immediately posthemorrhage were calculated by subtracting the volume of withdrawn blood from the baseline value. On the basis of the assumption that hemorrhage and subsequent volume resuscitation would not cause any hemolysis (as confirmed in group 1), all plasma Hb was considered to represent infused HBOC. The calculation of CBV using HBOC as an indicator was performed as previously published by Kasuya et al. CBV values derived from measured HBOC concentrations in plasma were compared with calculated (based on an original CBV of 85 mL/kg and withdrawn blood volume) values of CBV using the Bland-Altman analysis and by linear correlation. Agreement between the methods was analyzed by calculating the bias estimated by the mean difference and the standard deviation of the difference. Calculated and measured CBV values were highly correlated (r = 0.97). The difference between indicator dilution-derived and calculated values of CBV did not exceed 4% of calculated CBV in 97% of the measurements. The mean difference between measured and calculated values of CBV was 72 +/- 16 mL and did not vary significantly among groups 2, 3, and 4 (at varying concentrations of HBOC infused). In a canine hypovolemia model, knowing both the HBOC volume infused and the HBOC concentration measured in plasma allows for reliably determining the CBV. Our data verify the indicator-dilution technique with HBOC as an appropriate and clinically valuable method for monitoring CBV in treatment of hypovolemia.