refludan and Shock--Septic

Incidence of deep vein thrombosis in critically ill patients depends on the underlying disease but may be as high as 60%. The Surviving Sepsis Campaign clearly recommends administering anticoagulation in the absence of specific contraindications in patients with severe sepsis or septic shock. The article discusses risk factor for thromboembolic events in critical illness as well as means of non-pharmacologic and pharmacologic thrombosis prophylaxis. Peripheral vasoconstriction, edema, shock, and administration of catecholamines may reduce the bioavailability and efficacy of subcutaneous administration of low molecular weight heparin. This article further elaborates on the problem and pathophysiology of heparin resistance. Continuous intravenous administration of new anticoagulants may be a promising alternative to indirect anticoagulants. Severity of illness and SAPS II-score determine dosing of the direct thrombin inhibitor argatroban which needs to be about 10-times lower than in patients without critical illness.

Topics: Anticoagulants; Arginine; Biological Availability; Chromosome Breakage; Chromosome Disorders; Critical Care; Dose-Response Relationship, Drug; Drug Resistance; Heparin; Heparin, Low-Molecular-Weight; Hirudins; Humans; Infusions, Intravenous; Injections, Subcutaneous; Pipecolic Acids; Recombinant Proteins; Risk Factors; Sepsis; Severity of Illness Index; Shock, Septic; Sulfonamides; Thrombin; Thrombocytopenia; Venous Thrombosis

We evaluated the endothelin-1 (ET-1) and thrombin involvement in cardiovascular and respiratory dysfunction during endotoxic shock in 18 anaesthetized, mechanically ventilated pigs, divided into three groups. Group 1 was pre-treated only with lipopolysaccharide (LPS), group 2 was treated with lepirudin, a thrombin inhibitor, group 3 was pre-treated with bosentan, a dual inhibitor of ET-1 receptors. Results show that LPS caused systemic hypotension, pulmonary biphasic hypertension, increase in lung resistances (R(L)) and decrease in compliance (C(L)). Lepirudin partially reduced the LPS-dependent pulmonary hypertension, without affecting the changes in C(L) and R(L). On the contrary, bosentan completely abolished the pulmonary hypertension and the changes inC(L) and R(L), and worsened the LPS-dependent systemic hypotension. Our results show that ET-1 is largely responsible for pulmonary derangement due to endotoxic shock; at bronchial level, the ET-1 release seems due only to LPS, while, at pulmonary vascular level, it results also from LPS-dependent thrombin activation.

Topics: Animals; Antihypertensive Agents; Bosentan; Cardiovascular System; Endothelin-1; Female; Fibrinolytic Agents; Hemodynamics; Hirudins; Lipopolysaccharides; Lung; Male; Recombinant Proteins; Respiratory System; Shock, Septic; Sulfonamides; Swine; Thrombin; Time Factors