Efficacy of FDA-approved hemostatic drugs to improve survival and reduce bleeding in rat models of uncontrolled hemorrhage

Ryan, Kathy L.; Cortez, Douglas S; Dick, Edward J.; Pusateri, Anthony E.

doi:10.1016/j.resuscitation.2005.11.008

Cited by 19 publications

(19 citation statements)

References 33 publications

(34 reference statements)

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“…45 In the cut tail model of the rat, neither tranexamic acid nor desmopressin had such an effect when given approximately 5 min before hemorrhage was induced. 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.…”

Section: Hemostatic Dressings and Drugsmentioning

confidence: 94%

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: Hemostatic Dressings and Drugsmentioning

confidence: 94%

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

Hahn

2012

Acta Anaesthesiol Scand

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“…This type of model is viewed as the most appropriate when investigating potential modulations of the reflex response to blood loss, where it is essential that the degree and rate of blood loss are the same between experimental groups (24). An uncontrolled hemorrhage model (25,26) would be inappropriate in this type of study because the altered pattern of blood loss could introduce a systematic bias between groups. It would not be possible to determine whether any difference in pattern of response to blood loss was due to, or resulted from, the difference in profile of blood pressure change during hemorrhage.…”

Section: Experimental Modelmentioning

confidence: 99%

Modification of acute cardiovascular homeostatic responses to hemorrhage following mild to moderate traumatic brain injury

McMahon

Kenny

Bennett

et al. 2008

Critical Care Medicine

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“…Desmopressin is an inexpensive drug with immediate onset and few and mild adverse effects (Lethagen, 1997). A high dose (10 times the standard in man) was used to compensate for the higher drug clearance in the rat and the possible loss of drug of rebleedings (Ryan et al, 2006). In conclusion, the results from our ''one vessel injury model,'' using three different i.v.…”

Section: Heinius Et Almentioning

confidence: 94%

“…Among the drugs tested as adjuncts to decrease the bleeding, recombinant-activated Factor VIIa (Ryan et al, 2006;Dutton and Conti, 2009) and tranexamic acid (Roberts et al, 2011) shows promising results. Studies in vitro indicate that desmopressin reverse the HT-induced impairment of the primary hemostasis (Ying et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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

Heinius

Sondén

Hahn

2012

Therapeutic Hypothermia and Temperature Management

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Efficacy of FDA-approved hemostatic drugs to improve survival and reduce bleeding in rat models of uncontrolled hemorrhage

Cited by 19 publications

References 33 publications

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

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

Modification of acute cardiovascular homeostatic responses to hemorrhage following mild to moderate traumatic brain injury

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

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