Compositional, structural, and functional alterations in pulmonary surfactant in surgical patients after the early onset of systemic inflammatory response syndrome or sepsis.

OBJECTIVES: Sepsis is one of the most important predisposing factors for the development of the acute respiratory distress syndrome (ARDS). Alterations of pulmonary surfactant contribute in the pathogenesis of ARDS. However, little is known about surfactant in patients with less severe grades of lung injury related to sepsis or systemic inflammatory response syndrome (SIRS). Therefore, the purpose of this study was to characterize endogenous surfactant in surgical intensive care patients with sepsis or SIRS.
DESIGN: Prospective, observational study.
SETTING: University-affiliated, interdisciplinary intensive care unit. PATIENTS: Eleven patients after major surgery with SIRS or sepsis included within 12 hrs of onset and 11 controls without infection or lung disease.
INTERVENTIONS: Operating room and standard intensive care unit management.
MEASUREMENTS AND MAIN RESULTS: Four serial bronchoalveolar lavage samples (BAL) were recovered over 7 days from the patients and single BAL samples were obtained from controls. BAL cells, total protein, surfactant-associated protein A (SP-A), surfactant alveolar transition forms, and surface activity were analyzed. Two of 11 patients met criteria for acute lung injury and six of the 11 patients met ARDS consensus conference criteria but acute lung injury or ARDS was not persistent. The mean Pao2/F(IO)2 for the patients over 7 days was 253.2+/-15.1 (SEM) and Murray's lung injury score was 1.12+/-0.12, indicating mild-to-moderate lung injury. BAL neutrophil counts were increased (p< .01), and the ratio of poorly functioning light aggregate surfactant to superiorly functioning heavy aggregate surfactant was increased compared with controls (0.32+/-0.06 vs. 0.09+/-0.01, p < .05). SP-A was decreased (1.9+/-0.4 vs. 3.5+/-0.6 microg/mL of BAL, p< .05) and there were increases in the ratios of phospholipid to SP-A (p < .05), protein to SP.A (p < .01), and protein to phospholipid (p < .05). The surface tension-lowering ability of purified heavy aggregate surfactant was significantly impaired (15.6+/-1.6 vs. 2.8+/-0.6 milliNewtons/m, p< .05).
CONCLUSIONS: These observations show that surgical patients with SIRS or sepsis who have mild-to-moderate lung injury develop surfactant dysfunction detectable within 7 days of onset. We propose, therefore, that therapeutic strategies to modulate these severe surfactant abnormalities should be considered, as these strategies may have the potential to reduce lung injury, which is associated with a high mortality in sepsis.