Bioavailability of oral fluconazole in critically ill abdominal trauma patients with and without abdominal wall closure: a randomized crossover clinical trial.

BACKGROUND: Patients with non-apposed fascial edges, known as laparostomy patients, have traditionally been given intravenous medications, because enteral absorption of medications was thought to be unpredictable. We hypothesized that critically ill patients with "open abdomens" would have bioavailability similar to that of matched patients with closed fascial edges. METHODS: Fluconazole, a commonly prescribed anti-fungal with good bioavailability was used as a marker of absorption. Postoperative abdominal trauma patients were enrolled in a case-control (laparostomy versus closed abdomen) crossover design study to receive either an oral or parenteral fluconazole (400 mg loading dose followed by 200 mg QD) for one week. After a washout period, the alternate route of administration was used for the second week. Blood levels were collected at the end of each week of therapy. Rectal swab stool specimens were cultured for fungi on days 0, 7, and 15. RESULTS: Sixteen patients were studied. The mean injury severity score was 23 (range 9-41). The bioavailability of enteral fluconazole was 51% +/- 30% in the open abdomen and 63% +/- 19% (p = 0.347) in the closed abdomen patients. There was great variation in the bioavailability between the individual patients, with a range of 30%-100% in both groups. Three patients developed rectal colonization with Candida krusei. CONCLUSION: The bioavailability of enterally dosed fluconazole was highly variable in both the open and closed abdomen patients. Intravenous administration of pharmaceuticals may provide more reliable serum levels in the first 2 weeks after trauma-related laparotomy.

Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury.

BACKGROUND: Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We tested the hypothesis that administration of rFVIIa early after injury would decrease bleeding and prolong the time from injury to death after experimental hepatic trauma. METHODS: Anesthetized swine were cannulated for blood sampling and hemodynamic monitoring. Avulsion of the left median lobe of the liver induced uncontrolled hemorrhage. After a 10% reduction in mean arterial pressure, animals (n = 8 per group) were blindly randomized to receive intravenous rFVIIa 180 microg/kg, rFVIIa 720 microg/kg, or placebo. Pathologic examination of brain, lung, kidney, heart, and small bowel was performed to assess intravascular thrombosis. RESULTS Mortality during the first hour was 50% (four of eight) in controls versus 0% with rFVIIa 720 microg/kg (p = 0.02, chi2). Blood loss was decreased in the rFVIIa 720 microg/kg group versus the placebo group (13.2 +/- 5.5 mL/kg vs. 21.9 +/- 7.7 mL/kg;p = 0.0223). Time from injury to death was significantly prolonged in the rFVIIa 720 microg/kg group compared with placebo (116 minutes vs. 8.5 +/- 3.5 minutes; p= 0.02). No macro- or microthrombi in vital organs were identified on pathologic examination. CONCLUSION: Intravenous administration of high-dose rFVIIa early after induction of hemorrhage decreased bleeding and prolonged survival. No evidence of thrombosis in vital organs was observed.