Pulmonary and Oxygen Transport Effects of Intravenously Administered Endotoxin in Normal Humans

Abstract
Little data are available describing the initial changes in pulmonary function and oxygen transport during human endotoxemia. We studied 26 normal humans after intravenously administered endotoxin (4 ng/kg). To evaluate alterations in gas exchange, hemodynamic monitoring was performed in nine subjects given endotoxin and six subjects given saline only. Compared with the control subjects, no changes in gas exchange occurred at 3 h, but after volume loading (mean, 2.2 L saline infused from 3 to 5 h) the PaCO2 fell (86.1 ± 2.3 mm Hg, p = 0.042), and the AaPO2 widened (18.5 ±1.7 mm Hg, p = 0.005). Oxygen consumption and delivery both increased significantly at 3 h (219 ± 17 and 1,030 ± 43 ml/min·min2) and 5 h (203 ± 7 and 949 ± 48 ml/min·min2) (p < 0.035), whereas oxygen extraction fell at 3 h (p = 0.041). Seventeen subjects underwent bronchoalveolar lavage 14 ± 4 days before and at 1.5 to 3 h (n = 8) or 5 h after (n = 9) the administration of endotoxin. No increase in the total number of cells or percent or absolute number of neutrophils was found at either time point. The rate of clearance of inhaled 99mTc-diethylenetriamine pentacetate aerosol, a measure of alveolar epithelial permeability, increased in subjects scanned before 3 h (n = 8; p < 0.05), whereas no significant changes occurred in subjects scanned 5 h after endotoxin (n = 5) or in control subjects (n = 6). Early inflammatory responses after intravenous administration of endotoxin to normal humans result in alterations in gas exchange and lung permeability. Because these changes occur without an increase in alveolar neutrophils, they may represent an effect of nonalveolar parenchymal neutrophils or they may occur by non-neutrophil-dependent mechanisms. Early responses of oxygen transport variables during endotoxemia include a hyperdynamic cardiovascular state, with increased oxygen consumption, and a normal capacity to utilize oxygen. These changes may represent some of the early alterations in human pulmonary function and oxygen transport that occur at the onset of gram-negative infections.