Inadequacy of low‐volume resuscitation with hemoglobin‐based oxygen carrier hemoglobin glutamer‐200 (bovine) in canine hypovolemia

Abstract

Stroma-free hemoglobin-based oxygen carriers (HBOC) have been developed to overcome problems associated with transfusion of allogeneic blood. We have studied the efficacy of the first licensed veterinary blood substitute, hemoglobin glutamer-200 bovine (Oxyglobin; Biopure, Cambridge, MA, USA, Hb-200), in a canine model of acute hypovolemia and examined whether clinically commonly used criteria are adequate to guide fluid resuscitation with this product. Twelve anesthetized dogs were instrumented for measurements of physiological variables including hemodynamic, oxygenation, and blood gas and acid-base parameters. Dogs were bled to a mean arterial pressure (MAP) of 50 mmHg for 1 h followed by resuscitation with either shed blood (controls) or Hb-200 until heart rate (HR), MAP and central venous pressure (CVP) returned to baseline. Recordings were repeated immediately and 3 h after termination of fluid resuscitation. Hemorrhage (average 32 mL/kg) caused significant decreases in total hemoglobin (Hb), mean pulmonary arterial pressure (PAP), cardiac output (CO) and oxygen delivery (DO2I), increases in HR and systemic vascular resistance (SVRI), and lactic acidosis. In controls, only re-transfusion of all shed blood returned HR, MAP and CVP to prehemorrhage values, whereas in other dogs this endpoint was reached with infusion of 10 mL/kg Hb-200. Unlike blood transfusion, Hb-200 infusion failed to return CI and DO2I to baseline and to increase arterial oxygen content (CaO2) and total Hb; SVRI further increased. Thus, commonly used criteria (HR, MAP, CVP) to guide transfusion therapy in patients posthemorrhage prove insufficient when HBOCs with pronounced vasoconstrictive action are used and lead to inadequate volume repletion.

Arterial oxygenation and oxygen delivery after hemoglobin-based oxygen carrier infusion in canine hypovolemic shock: A dose-response study

“…It shares most properties with Hb glutamer-250 (bovine; Hemopure [formerly HBOC-201], Biopure) (7), which is currently in phase III clinical trials and approved for use in humans in South Africa. Previous studies with low doses of Hb-200 (8,9) and HBOC-201 (10) revealed an improvement of hemodynamic functions, yet a significantly smaller increase in arterial oxygen content and oxygen delivery after HBOC infusion than expected based on the amount of Hb administered. Therefore, in the present study, our primary goal was to analyze whether infusion of Hb-200 will dosedependently and to a greater extent than conventional plasma expanders increase systemic oxygen delivery and tissue oxygenation in dogs subject to isovolemic resuscitation after acute blood loss.…”

“…Methods were essentially as described and discussed in detail previously (8,9) with modifications mentioned below.…”

“…Cardiac output was continuously monitored (Critical Care Systems QVUE, Oximetrix 3, Abbott Laboratories) and also assessed at baseline, posthemorrhage, resuscitation I, and resuscitation II by thermodilution in triplicate using 10 mL of saline (21°C). Body temperature was maintained at 38°to 39°C (8,9). Dogs were splenectomized after a midline laparotomy (8,9).…”

Avaliação hemodinâmica e metabólica da cetamina e cetamina S(+) após a reposição volêmica com hidroxietilamido 130/0,4 e solução salina hipertônica 7,5%

“…A esplenectomia foi realizada como medida complementar para anular o efeito da espleno-contração na fase compensatória do choque, sendo que, em cães, este órgão pode contribuir, durante esta fase, liberando sangue retido em seu parênquima (DRIESSEN et al, 2001).…”

Mensuração de pressão venosa central por meio de cateteres venosos central e periférico: comparação entre os valores obtidos em cães e elaboração de índice de correção

“…A PVC é um importante parâmetro de monitorização nas mais diversas situações clínicas (IMPERATORE et al, 2002;ONDA et al, 2003) e experimentais (PITTARD & VUCEVIC, 1998;DRIESSEN et al, 1999;SEZAI et al, 1999;CASTA et al, 2000;ERB et al, 2000;DRIESSEN et al, 2001;KUMAR, SOBTI & SINGH, 2001;LICK et al, 2001;LOZANO, CASTRO & RODRIGO, 2001;WATTERS et al, 2001;WIESENACK et al, 2001;VOSS et al, 2002). AMAR et al (2001) citam que pacientes submetidos a procedimentos cirúrgicos não cardíacos freqüentemente requerem monitoração por PVC para se obter informações acerca do estado de volume circulante e função cardíaca.…”