The Pathophysiology and Management of Hemorrhagic Shock in the Polytrauma Patient.

The recognition and management of life-threatening hemorrhage in the polytrauma patient poses several challenges to prehospital rescue personnel and hospital providers. First, identification of acute blood loss and the magnitude of lost volume after torso injury may not be readily apparent in the field. Because of the expression of highly effective physiological mechanisms that compensate for a sudden decrease in circulatory volume, a polytrauma patient with a significant blood loss may appear normal during examination by first responders.

Optimizing transfusion strategies in damage control resuscitation: current insights.

From clinical and laboratory studies of specific coagulation defects induced by injury, damage control resuscitation (DCR) emerged as the most effective management strategy for hemorrhagic shock. DCR of the trauma patient who has sustained massive blood loss consists of 1) hemorrhage control; 2) permissive hypotension; and 3) the prevention and correction of trauma-induced coagulopathies, referred to collectively here as acute coagulopathy of trauma (ACOT). Trauma patients with ACOT have higher transfusion requirements, may eventually require massive transfusion, and are at higher risk of exsanguinating.

Clot dynamics and mortality: The MA-R ratio.

Introduction: The coagulopathy of trauma, illustrated by a short R-time, is common and well understood. The physiology behind this may be early thrombin burst with rapid clot formation. Rapid consumption of fibrinogen, however, may result in weak clot and substrate depletion, resulting in low MA.

1: 1 Transfusion strategies are right for the wrong reasons.

Background: Early assessment of clot function identifies coagulopathies after injury. Abnormalities include a hypercoagulable state from excess thrombin generation, as well as an acquired coagulopathy. Efforts to address coagulopathy have resulted in earlier, aggressive use of plasma emphasizing 1:1 resuscitation.

Damage Control Resuscitation for Catastrophic Bleeding.

The timely recognition of shock secondary to hemorrhage from severe facial trauma or as a complication of complex oral and maxillofacial surgery presents formidable challenges. Specific hemostatic disorders are induced by hemorrhage and several extreme homeostatic imbalances may appear during or after resuscitation. Damage control resuscitation has evolved from massive transfusion to a more complex therapeutic paradigm that includes hemodynamic resuscitation, hemostatic resuscitation, and homeostatic resuscitation.

Damage control resuscitation.

The early recognition and management of hemorrhage shock are among the most difficult tasks challenging the clinician during primary assessment of the acutely bleeding patient. Often with little time, within a chaotic setting, and without sufficient clinical data, a decision must be reached to begin transfusion of blood components in massive amounts. The practice of massive transfusion has advanced considerably and is now a more complete and, arguably, more effective process.

Protease-activated receptor-1 contributes to cardiac remodeling and hypertrophy.

Background: Protease-activated receptor-1 (PAR-1) is the high-affinity receptor for the coagulation protease thrombin. It is expressed by a variety of cell types in the heart, including cardiomyocytes and cardiac fibroblasts. We have shown that tissue factor (TF) and thrombin contribute to infarct size after cardiac ischemia-reperfusion (I/R) injury.

Toll-like receptor 4 mediates lung ischemia-reperfusion injury.

Background: We have previously reported that nuclear factor (NF)-kappaB activation and inflammatory cytokine expression were involved in the development of lung ischemia-reperfusion injury (LIRI). Because Toll-like receptor 4 (TLR4) activates NF-kappaB-dependent transcription of inflammatory cytokine genes during myocardial ischemia-reperfusion injury, we examined whether absence of TLR4 in TLR4-deficient mice protects against LIRI.

Methods: Left lungs of wild-type (C57BL/6J) mice or TLR4-null (TLR4-/-) mice were made ischemic for 60 minutes and then reperfused for 180 minutes.

Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion injury.

Background: We previously reported that the functional mutation of Toll-like receptor 4 (TLR4) in C3H/HeJ mice subjected to myocardial ischemia-reperfusion (MI/R) injury resulted in an attenuation of myocardial infarction size. To investigate the ligand-activating TLR4 during MI/R injury, we evaluated the effect of eritoran, a specific TLR4 antagonist, on MI/R injury, with the goal of defining better therapeutic options for MI/R injury.

Methods And Results: C57BL/6 mice received eritoran (5 mg/kg) intravenously 10 minutes before 30 minutes of in situ of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion.

Sacral resection and reconstruction for tumors and tumor-like conditions.

Sacrectomy is intended to resect aggressive local and life-threatening disease. Reconstruction can be difficult. This article reports on the use of sacrectomy for tumor and tumor-like conditions.

Specific inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates vascular proliferation in monocrotaline-induced pulmonary hypertension in rats.

Objectives: p38 mitogen-activated protein kinase is associated with many clinical entities characterized by inflammation. We postulated that inhibition of p38 mitogen-activated protein kinase with FR167653 attenuates inflammation and the development of pulmonary hypertension in monocrotaline-treated rats.

Methods: Rats were divided into 4 groups: (1) the control group (daily 0.

FR167653 diminishes infarct size in a murine model of myocardial ischemia-reperfusion injury.

Objective: During myocardial ischemia-reperfusion injury, p38 mitogen-activated protein kinase is activated. We examined the effect of a highly specific inhibitor of p38 mitogen-activated protein kinase, FR167653, in an experimental model of regional myocardial ischemia-reperfusion.

Methods: CD-1 mice received FR167653 intraperitoneally 24 hours before 30 minutes of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion.

Toll-like receptor 4 mediates ischemia/reperfusion injury of the heart.

Background: Restoration of blood flow to the ischemic heart may paradoxically exacerbate tissue injury (ischemia/reperfusion injury). Toll-like receptor 4, expressed on several cell types, including cardiomyocytes, is a mediator of the host inflammatory response to infection. Because ischemia/reperfusion injury is characterized by an acute inflammatory reaction, we investigated toll-like receptor 4 activation in a murine model of regional myocardial ischemia/reperfusion injury.

HSP70.1 and -70.3 are required for late-phase protection induced by ischemic preconditioning of mouse hearts.

We investigated the role of inducible heat shock proteins 70.1 and 70.3 (HSP70.

Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury.

Reperfusion of the ischemic heart is necessary to prevent irreversible injury of the myocardium, which leads to permanent organ dysfunction. However, reperfusion in itself leads to myocardial ischemia/reperfusion (I/R) injury, which is characterized by an acute inflammatory response mediated by activated inflammatory cells, chemokines, cytokines, and adhesion molecules. The molecular mechanisms of myocardial I/R injury are not completely known.

Nuclear factor kappaB mediates a procoagulant response in monocytes during extracorporeal circulation.

Objective: The objective of this study was to examine the mechanism of procoagulant activity and inhibition in whole blood during extracorporeal circulation.

Methods: In this study we examine the development of procoagulant activity and monocyte activation in heparinized whole blood passing through a closed circuit consisting of a pump and silicone envelope membrane oxygenator for 6 hours.

Results: Anaphylatoxins, C3a and C5a, determined by means of enzyme-linked immunosorbant assay, appeared in the blood within 30 minutes of circulation.