Guidelines for drotrecogin alfa (activated) — Xigris
Guidelines for drotrecogin alfa (activated) — Xigris
Indication: Severe sepsis as demonstrated by the following:
Patient has known or suspected infection.
Such as white blood cell counts in a normally sterile body fluid, perforated viscus, chest x-ray consistent with pneumonia, and production of purulent sputum.
AND
Patient has three of the four sytemic infection response syndrome criteria:
- Body temperature > 38º C (100.4º F) or < 36º C (96.8º F);
- Heart rate > 90 beats/min except in patients with a medical condition known to increase heart rate or those receiving treatment that would prevent tachycardia;
- Respiratory rate > 20 breaths/min or a PaCO2 < 32 mmHg or mechanical ventilation; and
- White blood cell count of > 12,000/mm3 or < 4,000/mm3 or > 10% bands.
AND
Evidence of at least one of the following signs of organ dysfunction due to sepsis that has been present for no longer than 24 hours:
• Cardiovascular
An arterial systolic blood pressure < 90 mmHg or a mean arterial blood pressure (MAP) < 70 mmHg for at least one hour despite adequate fluid resuscitation, adequate intravascular volume status, or the need for vasopressors to maintain systolic blood pressure > 90 mmHg or MAP > 70 mmHg.
• Renal
Urine output < 0.5 mL/kg/hr for one hour despite adequate fluid resuscitation.
• Respiratory
PaO2/FiO2 < 250 in the presence of other dysfunctional organs or < 200 if lung is only dysfunctional organ.
• Hematology
Platelet count of < 80,000/mm3 or a 50% decrease in the platelet count over the previous three days.
• Metabolic acidosis
pH < 7.3 or base deficit > 5 mmol/L with a lactate level > 1.5 times the upper limit of normal.
Situations in which drotrecogin alfa (activated) is not indicated:
- Mild-to-moderate sepsis without evidence of end-organ dysfunction;
- Moribund patients in whom death is imminent; and
- Patients whose families or physician is not committed to the aggressive management of their underlying medical condition, i.e., do-not-resuscitate status.
Contraindications: (final criteria pending approval of product labeling)
- Pregnancy or breast feeding;
- Age < 18 years;
- Weight > 135 kg;
- Platelet count < 30,000/mm3;
- Active bleeding at any site;
- Recent surgery or trauma with uncertain hemostasis;
- Known hypercoagulable condition;
- Recent (within three months) deep vein thrombosis or pulmonary embolism;
- Severe head trauma, intracranial or spinal surgery, or stroke within three months;
- History of bone marrow, kidney, small bowel, liver, lung, or pancreas transplantation;
- Human immunodeficiency virus infection in association with a last known CD4 count of < 50/mm3;
- Chronic renal failure requiring hemodialysis or peritoneal dialysis (acute renal failure is not a contraindication);
- Known or suspected portosystemic hypertension, chronic jaundice, cirrhosis, or chronic ascites;
- Acute pancreatitis with no established source of infection.
Use any of the following medications or treatment regimens:
- Unfractionated heparin to treat an active thrombotic event within eight hours (prophylactic heparin < 15,000 units/d permitted);
- Low molecular weight heparin at a higher dose than recommended for prophylactic use within 12 hours;
- Warfarin use within seven days;
- Aspirin use > 650 mg/d within three days;
- Thrombolytic use within three days (catheter clearance use is permitted);
- Glycoprotein IIb/IIIa antagonists within seven days;
- Antithrombin III at a dose > 10,000 units within 12 hours.
Dosing:
Pending approval of final labeling, 24 mcg/kg/hr is infused for 96 hours. The infusion is stopped one hour before any percutaneous procedure or major surgery and resumed one hour or 12 hours later, respectively, in the absence of bleeding complications.
Numbers to treat:
- To save one life: 16;
- To have one serious bleeding complication: 66.
Cost:
The current estimate is $5,000-$7,000 for an average course of treatment.
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