Showing papers by "Gordon R. Bernard published in 1987"

High-dose corticosteroids in patients with the adult respiratory distress syndrome.

Abstract: Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.

Perilla ketone: a model of increased pulmonary microvascular permeability pulmonary edema in sheep.

Abstract: A model of increased microvascular permeability pulmonary edema was developed in chronically instrumented unanesthetized sheep using perilla ketone (PK). PK did not cause changes in pulmonary hemodynamics but did cause marked increases in the flow of protein-rich lung lymph. The changes in lung lymph flow were accompanied by radiographic evidence of both interstitial and alveolar pulmonary edema as well as hypoxemia. PK did not cause acute changes in lung mechanics. Dynamic compliance of the lungs and FRC decreased later, concomitant with the changes in lung lymph flow, radiographic evidence for pulmonary edema, and hypoxemia. Resistance to air flow across the lungs and specific conductance did not change significantly after PK infusion. The severity of the radiographic evidence for pulmonary edema observed after PK correlated with the severity of the concomitant hypoxemia and changes in dynamic compliance of the lungs. PK did not cause increases in the concentrations of cyclooxygenase products of arachidonic acid in lung lymph or plasma or changes in blood leukocyte counts. We conclude that PK causes increased lung microvascular permeability pulmonary edema without acute changes in pulmonary hemodynamics. This model permits study of the pathophysiologic aspects of increased lung microvascular permeability without the concomitant functional alterations that complicate most other experimental models of diffuse lung injury.

Vancomycin entry into lung lymph in sheep.

Abstract: The distribution of antibiotics into target tissues is a crucial factor in therapeutic efficacy To estimate the availability of systemically administered vancomycin to the interstitial fluid in the lung, we have used a sheep model with a chronic pulmonary lymph fistula to collect simultaneously series of plasma and pulmonary lymph specimens during a 6-h period after an intravenous dose of vancomycin (7 mg/kg) After a minor delay in transit from blood to lymph, vancomycin was completely distributed to pulmonary lymph with a ratio of free drug in lymph to free drug in plasma of 09 This suggests that vancomycin is an excellent choice for treating pulmonary infections by susceptible organisms