Other Therapies

BICARBONATE Some investigators advocate the administration of bicarbonate for individuals with severe acidosis (pH <7.2). The efficacy of this intervention is not established.

THERAPY OF DIC The management of the patient in DIC has three basic approaches: elimination of the underlying disorder or source of infection; substitution of coagulation constituents lost in the clotting process; and arrest of the intravascular clotting process. If the patient is actively bleeding and decompensated DIC is present, urgent replacement of the components of the coagulation and fibrinolytic systems is indicated with the rapid infusion of fresh-frozen plasma and/or platelets. Reasonable guidelines in the actively bleeding patient with DIC include the transfusion of platelets to maintain a concentration of 50 to 100 * 10 3/pL and fresh-frozen plasma to keep the coagulation parameters (prothrombin time and activated prothrombin time) less than twice normal.

Interruption of the activated hemostatic system has been attempted by a number of investigators. Heparin has been used (primarily outside the United States) with mixed results. Currently, no conclusive evidence is available to suggest that heparin therapy reduces morbidity or mortality in septic patients with DIC. Administration of a natural anticoagulant, such as antithrombin III (ATIII) may arrest clotting without concomitant risk of bleeding. ATIII is a single-chain glycopeptide that is produced by the liver. ATIII is an important regulator of hemostasis by inhibiting several serine proteases of the coagulation system, predominately thrombin and factor Xa. Plasma ATIII levels decrease in septic patients with DIC. In healthy individuals, the half-life of ATIII is approximately 60 h. In patients with sepsis and septic shock, this may be reduced to as little as 4 to 6 h. The possibility that replacement of ATIII neutralizes excess thrombin and dampens the intravascular coagulation process has prompted several experimental and clinical studies. In several animal models of DIC, infusion of ATIII concentrates shortened the duration of DIC and reduced multiple organ failure and mortality. Results of human clinical studies have been mixed. These investigations have suggested either a trend towards efficacy or no significant difference between patients who received ATIII and controls. Until a definitive study is available, some experts recommend that patients with DIC secondary to a septic process should receive replacement of ATIII to a level of 70 to 80 percent of normal. Other investigators suggest that a much higher level of ATIII (140 to 150 percent) is required for efficacy.

ANTI-INFLAMMATORIES Although some animal models have shown that high-dose corticosteroid therapy was effective, large clinical trials have shown no differences in mortality between corticosteroid treated patients and control patients. These studies also have documented the occurrence of superinfection in corticosteroid treated patients. Thus the primary role of steroids is in patients with suspected or documented adrenal insufficiency. Adrenal insufficiency should be considered in septic patients with fulminant N. meningitidis bacteremia, disseminated tuberculosis, AIDS, prior glucocorticoid use, or with refractory hypotension. The use of inhibitors to metabolites elaborated in sepsis (inhibitors include ibuprofen, naloxone, eicosanoids, or antihistamines) has not proven to be effective in the management of septic shock.

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