Fluid Resuscitation of Uncontrolled Hemorrhage Using a Hemoglobin-Based Oxygen Carrier

White, Nathan J.; Wang, Xu; Bradbury, Nicole; Moon-Massat, Paula F.; Freilich, Daniel; Auker, Charles R.; McCarron, Richard M.; Scultetus, Anke; Stern, Susan A.

doi:10.1097/shk.0b013e31827fd62b

Cited by 20 publications

(9 citation statements)

References 32 publications

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“…This response may be attributed to an acute inflammatory reaction causing pulmonary vascular constriction mediated by pulmonary macrophages because depletion of pulmonary macrophages in swine has also been shown to eliminate the increase in PAP associated with endotoxin infusion (38). There was also no simultaneous increase in systemic vascular resistance (data not shown), decrease in blood pressure, or decreased cardiac output to suggest that the PAP response was a product of systemic vasoconstriction similar to that seen with infusion of hemoglobin-based oxygen carriers (HBOC’s) (20). The response may also be specific to fibrinogen because isolated rabbit lungs have also demonstrated vasoconstriction and a sharp rise in PAP when perfused with soluble fibrin/fibrinogen-oligomers (39).…”

Section: Discussionmentioning

confidence: 96%

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Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

White¹,

Wang²,

Liles

et al. 2014

Shock

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The purpose of this study was to evaluate the effect of fibrinogen concentrate, as a hemostatic agent, on limited resuscitation of uncontrolled hemorrhagic shock. We use a swine model of hemorrhagic shock with free bleeding from a 4mm aortic tear to test the effect of adding a one-time dose of fibrinogen concentrate given at the onset of limited fluid resuscitation. Immature female swine were anesthetized and subjected to catheter hemorrhage and aortic tear to induce uniform hemorrhagic shock. Animals (N=7 per group) were then randomized to receive either; 1. No fluid resuscitation (Neg Control), 2. Limited resuscitation in the form of two boluses of 10ml/kg of 6% hydroxyethyl starch solution (HEX) given 30 minutes apart, or 3. The same fluid regimen with one dose of 120mg/kg fibrinogen concentrate given with the first HEX bolus (FBG). Animals were then observed for a total of 6 hours with aortic repair and aggressive resuscitation with shed blood taking place at 3 hours. Survival to 6 hours was significantly increased with FBG (7/8, 86%) vs. HEX (2/7, 29%), and Neg Control (0/7, 0%) (FBG vs. HEX, Kaplan Meier LR p=0.035). Intraperitoneal blood loss adjusted for survival time was increased in HEX (0.4ml/kg/min) when compared to FBG (0.1mg/kg/min, p=0.047) and Neg Control (0.1ml/kg/min, p=0.041). Systemic and cerebral hemodynamics also showed improvement with FBG vs. HEX. Fibrinogen concentrate may be a useful adjunct to decrease blood loss, improve hemodynamics, and prolong survival during limited resuscitation of uncontrolled hemorrhagic shock.

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Section: Discussionmentioning

confidence: 96%

“…This research protocol was previously published in detail (20). Briefly, Immature female mixed breed Yorkshire swine were first sedated using intramuscular Ketamine (Bioniche Pharma, Galway, Ireland) and anesthetized throughout the protocol using inhaled 2% isoflurane (VetOne, Boise, ID).…”

Section: Methodsmentioning

confidence: 99%

Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

White¹,

Wang²,

Liles

et al. 2014

Shock

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“…The clinical application of the HBOCs has been limited by the toxic effect profile. However, investigations are ongoing into the use of these products ( 8 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of different types of fluid resuscitation on hepatic mitochondria and apoptosis

Cheng

Gao

et al. 2013

Experimental and Therapeutic Medicine

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The aim of this study was to observe the effects of different types of fluid resuscitation on hepatic mitochondria and apoptosis in hemorrhagic shock, and the corresponding mechanisms. Forty rats were divided into five groups: Sham surgery (Sham group), shock (Shock group), Ringer’s lactate resuscitation (RL group), hydroxyethyl starch resuscitation (HES group) and autologous blood resuscitation (BL group). A model of hemorrhagic shock was successfully induced in the latter four groups. The recovery objective was to maintain the mean arterial pressure (MAP) of the rats at 80 mmHg. Two hours after the end of the recovery experiment, fresh liver samples were examined in order to observe the changes in the morphology and mitochondrial membrane potential (ΔΨm). In addition, the levels of succinate dehydrogenase (SDH) activity were assessed, and a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was conducted to evaluate the level of apoptosis in the liver cells. In the Shock, RL, HES and BL groups, mitochondrial ultrastructural damage in the liver cells, significant reductions in liver cell function, liver ΔΨm and SDH activity, and the apoptosis of hepatocytes were more apparent compared with those in the Sham group. In the BL group, compared with the RL and HES groups, the injuries to the mitochondrial ultrastructure and liver cell function were significantly reduced, the hepatic ΔΨm and SDH activity were significantly increased and the hepatocyte apoptosis index (AI) was significantly reduced (P<0.05). In conclusion, in a rat model of hemorrhagic shock, different methods of fluid resuscitation may improve the liver cells with regard to mitochondrial ultrastructure and function, the stability of liver ΔΨm, the activity of SDH and the inhibition of liver cell apoptosis. The results indicate that infusion with autologous blood followed by RL solution is a preferable method of fluid resuscitation compared with HES.

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“…Following euthanasia at T360, the brain was fixed in 10% buffered formalin for ≥48 h prior to paraffin embedding. Brain sections (cranial (rostral) cerebrum parietal lobe, cranial (rostral) and caudal hippocampus, and cranial (rostral) brainstem/cerebellum) were stained with H&E or Fluoro-Jade-B to identify degenerating neurons [ 29 , 30 ].…”

Section: Methodsmentioning

confidence: 99%

Treatment of Swine Closed Head Injury with Perfluorocarbon NVX-428

et al. 2020

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Pre-hospital treatment of traumatic brain injury (TBI) with co-existing polytrauma is complicated by requirements for intravenous fluid volume vs. hypotensive resuscitation. A low volume, small particle-size-oxygen-carrier perfluorocarbon emulsion NVX-428 (dodecafluoropentane emulsion; 2% w/v) could improve brain tissue with minimal additional fluid volume. This study examined whether the oxygen-carrier NVX-428 shows safety and efficacy for pre-hospital treatment of TBI. Anesthetized swine underwent fluid percussion injury TBI and received 1 mL/kg IV NVX-428 (TBI-NVX) at 15 min (T15) or normal saline (no-treatment) (TBI-NON). Similarly, uninjured swine received NVX-428 (SHAM-NVX) or normal saline (SHAM-NON). Animals were monitored and measurements were taken for physiological and neurological parameters before euthanasia at the six-hour mark (T360). Histopathological analysis was performed on paraffin embedded tissues. Physiological, biochemical and blood gas parameters were not different, with the exception of a significant but transient increase in mean pulmonary artery pressure observed in the TBI-experimental group immediately after drug administration. There were no initial differences in brain oxygenation at baseline, but over time oxygen decreased ~50% in both TBI groups. Histological brain injury scores were similar between TBI-NVX and TBI-NON, although a number of subcategories (spongiosis-ischemic/dead neurons-hemorrhage-edema) in TBI-NVX had a tendency for lower scores. The cerebellum showed significantly lower spongiosis and ischemic/dead neuron injury scores and a lower number of Fluoro-Jade-B-positive cerebellar-Purkinje-cells after NVX-428 treatment compared to controls. NVX-428 may assist in mitigating secondary cellular brain damage.

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Fluid Resuscitation of Uncontrolled Hemorrhage Using a Hemoglobin-Based Oxygen Carrier

Cited by 20 publications

References 32 publications

Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

Fibrinogen Concentrate Improves Survival During Limited Resuscitation of Uncontrolled Hemorrhagic Shock in a Swine Model

Effects of different types of fluid resuscitation on hepatic mitochondria and apoptosis

Treatment of Swine Closed Head Injury with Perfluorocarbon NVX-428

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