title: Ketoconazole prevents acute respiratory failure in critically ill surgical patients.
abstract: Effective prophylaxis against acute respiratory failure (ARDS) has not been established. This study investigated whether or not ketoconazole could prevent ARDS in critically ill surgical patients. Seventy-one Surgical Intensive Care Unit (SICU) patients without liver dysfunction received either ketoconazole (n = 35), 200 mg daily via the gastrointestinal tract, or placebo (n = 36), for 21 days or until discharge from the SICU, in a prospective, randomized, double-blind study. Patients were monitored clinically for signs of ARDS, defined as all the following: intrapulmonary shunt greater than 15%, a PaO2/FIO2 ratio less than 150, normal central venous, pulmonary capillary wedge, or left atrial pressure, no other cause of hypoxemia, and a consistent chest X-ray. Thirteen patients (18%) developed ARDS with significantly increased mortality versus non-ARDS patients (69% vs. 29%). The incidence of ARDS was decreased among ketoconazole patients compared to placebo (6% vs. 31%; p less than 0.01), as was median SICU stay (7.0 days vs. 15.5 days; p less than 0.05), and median SICU cost (+5,600. vs. +12,400.; p less than 0.05). Mortality is increased with ARDS after trauma and surgery. We conclude that ketoconazole prevents ARDS, shortens SICU stay, and lowers hospital costs.
authors.affiliation: Department of Surgery, Brown University, Providence, RI.
authors.forename: G J
authors.initials: GJ
authors.lastname: Slotman
authors.forename: K W
authors.initials: KW
authors.lastname: Burchard
authors.forename: A
authors.initials: A
authors.lastname: D'Arezzo
authors.forename: D S
authors.initials: DS
authors.lastname: Gann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007654:Ketoconazole / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D011446:Prospective Studies; D011897:Random Allocation; D012128:Respiratory Distress Syndrome / Q000517:prevention & control*
chemical_list: D007654:Ketoconazole