Pharmacy & Therapeutics- August 2008 - (Page 472) CASE REPORT: Low-Dose Drotrecogin Alfa in Sepsis Appendix 1 Winthrop University Hospital Drotrecogin alfa Protocol Winthrop University Hospital Hospital-Wide Critical Care Committee Drotrecogin alfa (Xigris®) Order Form Drotrecogin alfa is a recombinant form of human activated protein C, which exerts an antithrombotic effect by inhibiting Factors Va and VIIIa. In vitro data indicate that activated protein C has indirect profibrinolytic activity through its ability to inhibit plasminogen activator inhibitor-1 (PAI-1) and limiting generation of activated thrombin–activatable–fibrinolysis– inhibitor. Additionally, in vitro data indicate that activated protein C may exert an anti-inflammatory effect by inhibiting human tumor necrosis factor production by monocytes, by blocking leukocyte adhesion to selectins, and by limiting the thrombin-induced inflammatory responses within the microvascular endothelium. The efficacy of drotrecogin alfa was studied in an international, multi-center, randomized, double-blind, placebo-controlled trial (PROWESS) of 1,690 patients with severe sepsis. In this trial, there was an absolute mortality reduction of 13% in drotrecogin alfa–treated patients who have APACHE II score of ≥25, compared to the placebo group. Similarly, absolute mortality reductions of 8% and 11% were also observed for patients with 3 or 4 organ failures, respectively. The efficacy of drotrecogin alfa has not been established in less severe patients (i.e., APACHE II score of <25; 2 organ failures or less). Note: Drotrecogin alfa can be ordered only after the prescribing critical care attending physician has seen the patient. Patient Name Date M. R. # ICU Room # Name of physician requesting drotrecogin alfa Name of physician approved the use Step 1. Inclusion criteria (circle all that apply, must meet criteria A or B, plus C and D) A. APACHE II score must be ≥25 and at least 1 of criteria in section B Or: B. Criteria of acute organ failure (must meet at least 3 of following 5 criteria) 1. Cardiovascular system dysfunction defined as: a. Shock, and b. Hypotension, and c. Need for vasopressor support despite adequate fluid resuscitation 2. Renal dysfunction defined as a. Oliguria (urine output <0.5 ml/kg of body weight/hour for 1 hour) despite adequate fluid resuscitation 3. Respiratory-system dysfunction defined as a. PaO2/FiO2 ratio ≤250 in the presence of other dysfunctional organs or systems –or– b. PaO2/FiO2 ratio ≤200 if the lung was the only dysfunctional organ 4. Hematological dysfunction defined as a. Platelet count <80,000/mm3 –or– b. Platelet decreased by 50% from the highest count in the previous 3 days c. Thrombocytopenia must be attributable to sepsis rather than medication or other disease 5. Unexplained metabolic acidosis with elevated lactic acid concentrations And: C. Infection criteria—known or suspected infection (1 or more below) a. White cells in a normally sterile body fluid –or– b. Perforated viscus –or– c. Radiographic evidence of pneumonia with purulent sputum –or– d. Syndrome associated with high degree of infection (i.e., ascending cholangitis) –or– e. Focus of infection has been visualized (surgical findings, purulent wound drainage, CT showing evidence of abscess) D. Modified SIRS criteria (must meet 3 of the 4 criteria below) a. Core temperature ≥ 38º C (100.4º F) or ≤36º C (96.8º F) –or– b. Heart rate ≥ 90 bpm (except other medical explanation, treatment to prevent tachycardia) –or– continued on page 475 472 P&T® • August 2008 • Vol. 33 No. 8
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