Effects of Different Fluid Regimes and Desmopressin on Uncontrolled Hemorrhage During Hypothermia in the Rat

Heinius, Göran; Sondén, Anders; Hahn, Robert G.

doi:10.1089/ther.2012.0006

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…26 When comparing the outcomes for various fluid programs during hypothermia, the results still supported those obtained by the cut tail cut modelmortality tended to be lower in large-and moderate-volume resuscitation with Ringer´s acetate solution compared to small-volume resuscitation, despite the fact that the rebleeding volume increased with the infused volume. 27 Hypothermia is well known to provoke coagulopathy. In white rabbits subjected to mild hypothermia (35 o C) followed by uncontrolled splenic injury, the tendency to develop coagulopathy was greater with hetastarch (MW 600 kD, Hextend) and dextran 70 compared to 5% human albumin.…”

Section: Body Temperaturementioning

confidence: 99%

“…46 In addition, desmopressin did not alleviate hemorrhage in the femoral artery model of hypothermic rats; here, the drug was injected 5 min after hypovolemic hypotension had been induced. 27 Recombinant-activated factor VII (rFVIIa; NovoSeven) has received the greatest attention among the hemostatic drugs. Several animal studies and smaller clinical trials of this procoagulant therapy have been published in the past decade.…”

Section: Hemostatic Dressings and Drugsmentioning

confidence: 99%

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Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Hahn

2012

Acta Anaesthesiol Scand

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Intravenous fluid is life-saving in hypovolemic shock, but fluid sometimes aggravates the bleeding. During the past 25 years, animal models have helped our understanding of the mechanisms involved in this unexpected effect. A key issue is that vasoconstriction is insufficient to arrest the bleeding when damage is made to a major blood vessel. ‘Uncontrolled hemorrhage’ is rather stopped by a blood clot formed at the outside surface of the vessel, and the immature clot is sensitive to mechanical and chemical interactions. The mortality increases if rebleeding occurs. In the aortic tear model in swine, hemorrhage volume and the mortality increase from effective restoration of the arterial pressure. The mortality vs. amount of fluid curve is U-shaped with higher mortality at either end. Without any fluid at all, irreversible shock causes death provided the hemorrhage is sufficiently large. Crystalloid fluid administered in a 3 : 1 proportion to the amount of lost blood initiates serious rebleeding. Hypertonic saline 7.5% in 6% dextran 70 (HSD) also provokes rebleeding resulting in higher mortality in the recommended dosage of 4 ml/kg. Uncontrolled hemorrhage models in rats, except for the ‘cut-tail’ model, confirm the results from swine. To avoid rebleeding, fluid programs should not aim to fully restore the arterial pressure, blood flow rates, or blood volume. For a hemorrhage of 1000 ml, computer simulations show that deliberate hypovolemia (−300 ml) would be achieved by infusing 600–750 ml crystalloid fluid over 20–30 min or 100 ml of HSD over 10–20 min in an adult male

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Section: Body Temperaturementioning

confidence: 99%

Section: Hemostatic Dressings and Drugsmentioning

confidence: 99%

Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Hahn

2012

Acta Anaesthesiol Scand

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“…Controls animals were given IgG (DAKO, Santa Clara, California, USA). The dose was based on a previous study in hemorrhaged rats 16. Each group consisted of 7 rats.…”

Section: Methodsmentioning

confidence: 99%

“…The dose was based on a previous study in hemorrhaged rats. 16 Each group consisted of 7 rats. No sham group was used in this experiment, since previous experiments with this model showed that rats do not survive the full duration of the experiment without any resuscitation.…”

Section: Randomizationmentioning

confidence: 99%

Treatment with ddAVP improves platelet-based coagulation in a rat model of traumatic hemorrhagic shock

Wirtz

Roelofs

Goslings

et al. 2022

Trauma Surg Acute Care Open

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ObjectivesTrauma-induced hemorrhagic shock is characterized by increased endothelial permeability and coagulopathy. Vasopressin analog ddAVP (desmopressin) acts by reorganizing and redistributing adhesive and tight junction molecules, enhancing endothelial barrier function. Furthermore, ddAVP increases von Willebrand factor (vWF) plasma levels and thereby potentially enhances platelet-based coagulation. The objective of this study was to assess whether the use of ddAVP results in improvement of both endothelial barrier function and platelet-based coagulation, thereby improving shock reversal and reduce organ failure in a rat model of trauma and transfusion.MethodsBlood products were prepared from syngeneic rat blood according to blood bank standards. Polytrauma was induced in Sprague Dawley rats by a fractured femur and crush injury to the intestines and liver. The rats were hemorrhaged until a mean arterial pressure of 40 mm Hg and transfused with RBCs, fresh frozen plasmas and platelets in a 1:1:1 ratio, and randomized to receive a single dose of ddAVP (n=7 per group). Blood samples were taken up to 6 hours after trauma to assess biochemistry, markers of endothelial injury and coagulation status by rotational thromboelastometry (ROTEM). Organ damage was assessed by histopathology.ResultsRats receiving ddAVP showed significantly better shock reversal compared with controls. Also, coagulation parameters remained stable in the ddAVP treated group, whereas rats in the control group showed deterioration of coagulation parameters, including decreased clot strength and decreased platelet functioning (89% (IQR 82% to 92%) of baseline values). Platelet count and vWF antigen levels at exsanguination did not differ between groups. ddAVP did not reduce markers of endothelial dysfunction nor markers of organ injury.ConclusionsThe use of ddAVP in a rat trauma-transfusion model improved shock parameters and ROTEM parameters of clot formation. However, this did not abrogate the amount of organ failure.Level of evidenceLevel III.

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The clinical setting

James¹,

Dyer²

2016

Clinical Fluid Therapy in the Perioperative Setting

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Effects of Different Fluid Regimes and Desmopressin on Uncontrolled Hemorrhage During Hypothermia in the Rat

Cited by 4 publications

References 35 publications

Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Fluid therapy in uncontrolled hemorrhage – what experimental models have taught us

Treatment with ddAVP improves platelet-based coagulation in a rat model of traumatic hemorrhagic shock

The clinical setting

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