Despite recent advances in intensive care medicine, acute lung injury and its more severe form, acute respiratory distress syndrome pose major therapeutic problems. While mechanical ventilation is integral to the care of these patients, its adverse consequences including ventilator-induced lung injury are determinants of disease progression and prognosis. Among several important ventilator parameters, the use of low tidal volumes is probably the most important feature of lung-protective mechanical ventilation. Intensivists should be trained to recognize acute lung injury and acute respiratory distress syndrome and encouraged to use low-tidal-volume ventilation in clinical practice. Alternative modes of ventilation such as high-frequency ventilation and prone position should be reserved for selected patients in whom conventional lung-protective ventilation strategies have failed.

Summary

Background and objective: Proinflammatory cytokines as well as nitric oxide (NO) play a major role in mediating the response to lipopolysaccharide (LPS). The present study tested the hypothesis that LPS induces proinflammatory cytokines in the lung via the Toll-like receptor 4 (TLR4)/CD14 signalling cascade. Methods: Control mice and TLR4-deficient (TLR4-D) mice were used to test TLR4-mediated effects of LPS. Both strains received either Escherichia coli LPS (20 mg kg−1 intraperitoneal) or saline and their lungs were collected at different time points. Pulmonary nuclear factor κB (NFκB) activation was investigated with electromobility shift assay. mRNA expression of inflammatory mediators and their corresponding receptors were detected with Ribonuclease Protection Assay. Protein expression was detected by ELISA and western blotting. Inducible NO synthase (iNOS) expression was monitored by RT-PCR and iNOS activity by conversion of l-arginine to citrulline. Immune cells were sampled by bronchoalveolar lavage (BAL) and classified. Results: LPS application induced CD14-, but not TLR4 protein expression in control mice. Activation of pulmonary NFκB was observed within 60 min in control, but not in TLR4-D mice. Six hours of LPS administration induced a significant increase in pulmonary tumour necrosis factor α-, interleukin-1β- and interleukin-6 mRNA and protein expression in control mice compared to TLR4-D mice. Furthermore, LPS induced a significantly higher increase of the iNOS expression and catalytic activity in control mice than in TLR4-D mice. BAL revealed an increase in total cell count in all LPS treated mice. Conclusion: Our findings suggest that TLR4 plays a key role for regulating the expression of relevant cytokines within the lung during endotoxic shock.

Summary

Introduction: We decided to investigate the pathogenesis of pulmonary ventilatory and radiographic abnormalities in patients after major vascular surgery. Patients and methods: Sixteen mechanically ventilated patients without heart failure were studied, within 3 h after major abdominal surgery. We measured extravascular lung water, intrathoracic, global end-diastolic and pulmonary blood volumes, 67Ga-transferrin pulmonary leak index and ventilatory and radiographic variables. The latter allowed computation of the lung injury score as a measure of lung injury. Results: The extravascular lung water was elevated (>7 mL kg−1) in 5 of 16 patients, while the pulmonary leak index was elevated in 11 patients and a supranormal extravascular lung water was associated with a high pulmonary leak index and higher extravascular lung water relative to intrathoracic blood volume or pulmonary blood volume. Patients were arbitrarily divided into those with a lung injury score >1 and ≤1, and only differed in the factors composing the score as well as in extravascular lung water divided by pulmonary blood volume. A lung injury score >1 was associated with a longer duration of mechanical ventilation. Conclusion: Our data suggest that mild, subclinical, pulmonary oedema is relatively common after major vascular surgery, mainly caused by increased pulmonary capillary permeability in the absence of overt heart failure. However, permeability oedema only partially contributes to postoperative lung injury score and need for mechanical ventilation, suggesting a major contribution by atelectasis.