Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs (original) (raw)
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Journal of Trauma: Injury, Infection & Critical Care, 2008
Background: Some hemoglobinbased oxygen carriers (HBOCs) improve outcome in animal models of hemorrhagic shock (HS) in comparison with standard asanguinous resuscitation fluids. Nevertheless, concern about intrinsic vasoactivity, linked in part to low-molecular weight (MW) hemoglobin (Hb), has slowed HBOC development. We assessed the impact of decreasing the low-MW Hb component of bovine HBOC on vasoactivity in severe HS. Methods: Anesthetized invasively monitored swine were hemorrhaged 55% blood volume and resuscitated with bovine HBOC containing 31% (31 TD [HBOC-301]), 2% (2 TD [HBOC-201]), or 0.4% (0.4 TD) low-MW Hb. Pigs received four 10 mL/kg infusions over 60 minutes, hospital arrival was simulated at 75 minutes, organ blood flow (BF) was evaluated by microsphere injection, and monitoring was continued for 4 hours followed by complete necrotic evaluation. Results: There were few differences between 2 TD and 0.4 TD. Thirty-one TD pigs had higher systemic and pulmonary blood pressure (BP), systemic vascular resistance index, and pulmonary artery wedge pressure, compared with 2 TD or 0.4 TD (p < 0.01); however, pigs in all groups had at least mildly elevated BP. Transcutaneous tissue oxygenation, base excess, and mixed venous oxygen saturation were similar across groups; lactate and methemoglobin were highest with 0.4 TD (p < 0.03). There were no group differences in BF. Over time, myocardial BF increased and hepatic BF decreased in all groups (for 31 TD, p < 0.05); renal BF was unchanged in all groups. There were no group differences in heart, lung, or liver histopathology, and survival. Conclusions: Although purification from 31% to 2% low-MW Hb content significantly decreased vasoactive responses, further purification to 0.4% had no additional clinically measurable effects in severe HS. If further diminution in HBOC vasoactivity is desired for use in HS, additional technical approaches may be required.
Military medicine
Thisstudy examines the effects of modified stroma-free hemoglobin solution as an oxygen-carrying volume support fluid. Dogs weresubjected to hemorrhagic shock to a meanarterial pressure (MAP) of 40 torr for 30 minutes, and then resuscitated with pyridoxalated polymerized stroma-free hemoglobin solution (SFHS-PP), lactated Ringer's (LR) solution, or autotransfusion (A) with shed blood. Although for the LR group, the MAP, cardiacoutput, and mixed venous p02 had lower means than forthe SFH8-PP and Agroups, analysis for MAP showed no difference between groups. Heartrate in the SFH8-PP and A groupswas lower than in the LR group. Following resuscitation with SFH8-PP, there wastransient elevation «7 days)of the liver enzyme SGOT and alkaline phosphatase «2 days). No SFH8-PP inducedrenal glomerular or tubular damage was detected by urine analysis. ThePTand PTT were abnormaland thrombocytopenia occurredafterSFH8-PP infusion. A transient leukopenia in the SFH8-PP dogs was followed by leukocytosis. Hypoglycemia occurred for 48 hours in the SFH8-PP group, but no other electrolyte abnormalities were noted in any group. Oxygen was carried in the plasma (SFH8-PP fraction) and off-loaded to the tissues. SFH8-PP carried almosthalf of the total oxygen content of the blood. Arterial and mixed venous p02 were maintained in the physiologic range. SFH8-PP functions well as a volume replacement and as an oxygen-carrying fluid for resuscitation from hemorrhagic shock without major toxicity; however, no demonstrated advantage of SFH8-PP over LR could be determined.
Intensive Care Medicine Experimental, 2022
Background: Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient's own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of noninvasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock. Methods: A model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30-40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one-and two-way ANOVA. Results: Each treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation (p = 0.014) and tended
Hemoglobin-based oxygen carriers for hemorrhagic shock
Resuscitation, 2012
Hemorrhagic shock is a pathologic state in which intravascular volume and tissue oxygen delivery are impaired, leading to circulatory collapse and cellular ischemia. Resuscitation with hemoglobin-based oxygen carriers (HBOCs) is appealing in that their use can both restore intravascular volume and tissue oxygenation, without the limitations in supply and immunomodulatory effects of packed red blood cells. However, the development of safe and effective agents has been elusive. In this article, we briefly discuss the major limitations of traditional resuscitative fluids which have driven the continued interest in HBOCs. We then review the history of early HBOC development and the modern understanding of their mechanisms of toxicity, which has informed the rational design of second-generation agents. Finally, we provide an overview of these second-generation HBOCs that are under active investigation or have recently completed phase 3 clinical trials.
Understanding the effects of oxygen administration in haemorrhagic shock
Nursing in Critical Care, 2011
Aims and objectives: The aim of this article is to provide a review of the literature regarding oxygen administration and the use of oxygen in patients experiencing haemorrhagic shock (HS). Results: Oxygen is administered to patients to assist them in maintaining oxygenation. The administration of oxygen is complex and varies significantly among patients. In order to optimize patient care, clinicians need to be aware of the potential effects, both beneficial and harmful, that oxygen can have on the body. Inclusion and exclusion criteria: Literature inclusion criteria for this article was any article (1995 to present) pertaining to oxygen administration and HS. Also included were articles related to tissue injury caused by an overabundance of free radicals with the administration of oxygen. Articles related to oxygen and wound healing, pollution, aerospace, food and industrial uses were excluded. Conclusions: This review of the literature provides an overview of the use of oxygen in clinical practice and HS. The harmful effects of oxygen are highlighted to alert the clinician to this potential when there is an overabundance of oxygen. Relevance to clinical practice: Oxygen is one of the most common drugs used in the medical community; however, the effects of oxygen on the body are not well understood. The use of oxygen if not prescribed correctly can cause cellular damage and death. Clinicians need to be more aware of the effects of oxygen and the damage it may cause if not administered properly.
JL: Normovolemic hemodilution improves oxygen extraction capabilities in endotoxic shock
2015
We studied the effects of normovolemic hemodilution on tissue oxygen extraction capabilities in a canine model of endotoxic shock. Eighteen anesthetized and mechanically ventilated dogs underwent normovolemic hemodilution with 6% hydroxyethyl starch solution to reach hematocrit (Hct) levels around 40, 30, or 20% before the administration of 2 mg/kg of Escherichia coli endotoxin. Cardiac tamponade was then induced by repeated injections of normal saline into the pericardial sac to reduce cardiac output and study whole body oxygen extraction capabilities. Whole body critical oxygen delivery was lower in the Hct 20% and 30% groups (8.4 Ϯ 0.4 and 10.4 Ϯ 0.7 ml ⅐ kg Ϫ1 ⅐ min Ϫ1 , respectively) than in the Hct 40% group (12.8 Ϯ 0.8 ml ⅐ kg Ϫ1 ⅐ min Ϫ1) (both P Ͻ 0.005). The whole body critical oxygen extraction ratio was higher in the Hct 30% and 20% groups (49.1 Ϯ 8.2 and 55.2 Ϯ 4.6%, respectively) than in the Hct 40% group (37.1 Ϯ 4.4 %) (both P Ͻ 0.05). Liver critical oxygen extraction ratio was also higher in the Hct 30% and 20% groups than in the Hct 40% group. The arterial lactate concentrations and the gradient between ileum mucosal PCO2 and arterial PCO2 were lower in the Hct 20% and 30% groups than in the Hct 40% group. We conclude that, during an acute reduction in blood flow during endotoxic shock in dogs, normovolemic hemodilution is associated with improved tissue perfusion and increased oxygen extraction capabilities. sepsis; hypoxia; oxygen availability; dog experiment; tonometry SEPTIC SHOCK IS ASSOCIATED with significant alterations in cellular oxygen utilization (1, 18, 26), even though oxygen delivery (Ḋ O 2) to the tissues is typically maintained or even increased. Microregional zones of hypoxia (8, 23), secondary to microcirculatory disturbances (12), have been incriminated in these alterations, in addition to altered cellular metabolism. A complex interaction between an increased release of many mediators, leukocyte activation, endothelial injury, and interstitial edema has been largely implicated in this