No abstract

We conducted a prospective, randomized, double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury, including the adult respiratory distress syndrome (ARDS), or improve mortality when administered early in septic shock. All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1, 1983 and August 29, 1986 were eligible for admission to the study if they had either (1) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values (in already hospitalized patients), or (2) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg (in newly admitted patients). Patients meeting these criteria were excluded if they (1) had severe immunodeficiency, (2) were less than 18 or greater than 76 yr of age, (3) had multilobar roentgenographic infiltrates, or (4) were already receiving corticosteroids. Eighty-seven patients enrolled in the study received either methylprednisolone, 30 mg/kg per dose, or mannitol placebo for a total of 4 doses every 6 h, following the presumptive diagnosis of septic shock. Of these patients, 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry. Thirteen of the patients who received methylprednisolone developed ARDS, compared to 14 patients who received placebo. Lesser degrees of parenchymal lung injury did not differ between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

In this prospective study of 45 patients, we tested the hypothesis that markedly elevated levels of plasma von Willebrand antigen (vWf-Ag) a marker of endothelial cell injury, might predict the development of acute lung injury in patients with nonpulmonary sepsis syndrome. Acute lung injury was quantified on a four-point scoring system. At the time of entry into the study, none of the 45 patients had evidence of lung injury. Subsequently, 15 patients developed lung injury and 30 patients did not develop lung injury. The mean plasma vWf-Ag level was markedly elevated in the 15 patients who developed lung injury compared with the 30 patients who did not develop lung injury (588±204 vs. 338±196, percentage of control, P < 0.01). Furthermore, a plasma vWf-Ag level 2 450 was 87% sensitive and 77% specific for predicting the development of acute lung injury in the setting of nonpulmonary sepsis. In addition, the combination of a plasma vWf-Ag > 450 and nonpulmonary organ failure at the time of entry into the study had a positive predictive value of 80% for acute lung injury. Also, a plasma vWf-Ag level > 450 had a positive predictive value of 80% for identifying nonsurvivors. Thus, in patients with nonpulmonary sepsis, an elevated level of plasma vWf-Ag is a useful, early biochemical marker of endothelial injury and it has both predictive and prognostic value. (J. Clin. Invest. 1990. 86:474-480.) Key words: endothelial cells * acute lung injury* von Willebrand antigen level * sepsis * adult respiratory distress syndrome -shock

We assayed serial plasma samples from 86 patients, who were enrolled in a prospective randomized trial of the effects of methylprednisolone (MPSS) in septic shock, for the presence of cytokine tumor necrosis factor (TNF) using an enzyme-linked immunosorbent assay. TNF was present in the plasma of 27 of the 74 patients with septic shock, but in only 1 of the 12 patients with shock due to other causes. TNF was detected with equal frequency in patients with shock from gram-negative or from gram-positive bacillary sepsis. TNF levels were highest on the initial sample and decreased significantly over the subsequent 24 h in both the patients treated with MPSS and in those given placebo. Patients with detectable TNF had a higher incidence and severity of the adult respiratory distress syndrome and a higher mortality rate than did patients without detectable TNF.