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Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction.

D Shane O'Mahony1, W Conrad Liles, William A Altemeier

  • 1Division of Pulmonary and Critical Care Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA. oshane@u.washington.edu

Critical Care (London, England)
|September 26, 2006
PubMed
Summary

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Minimally injurious mechanical ventilation combined with endotoxemia enhances lung inflammation and causes liver and kidney injury in mice, even without significant lung damage. This highlights the complex interplay between ventilation strategies and sepsis complications.

Area of Science:

  • Critical Care Medicine
  • Pulmonary Medicine
  • Immunology

Background:

  • Sepsis-induced multiple organ dysfunction syndrome (MODS) is a significant complication in mechanically ventilated patients with acute respiratory distress syndrome.
  • The precise relationship between mechanical ventilation and MODS remains incompletely understood.
  • Investigating the synergistic effects of ventilation and endotoxemia on inflammatory pathways is crucial for understanding organ injury.

Purpose of the Study:

  • To determine if a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia.
  • To investigate the induction of pro-inflammatory pathways in the lungs and systemic circulation.
  • To assess the resulting distal organ dysfunction and/or injury.

Main Methods:

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  • C57BL/6 mice were administered intraperitoneal Escherichia coli lipopolysaccharide (LPS).
  • Mice were subjected to mechanical ventilation with tidal volumes of 10 ml/kg for 6 hours (LPS + MV group).
  • Control groups included ventilation alone (MV), LPS alone (LPS), and neither (PBS).

    • Main Results:

    • Increased myeloperoxidase activity and chemokine concentrations (MIP-2, KC) in the lungs of the LPS + MV group.
    • Minimal alveolar epithelial permeability changes and lung histological injury in the LPS + MV group.
    • Significant liver and kidney injury in the LPS + MV group, correlated with increased plasma IL-6, TNF-alpha, KC, and MIP-2.

    Conclusions:

    • Non-injurious mechanical ventilation strategies interact with endotoxemia.
    • Pro-inflammatory mechanisms are enhanced in the lungs, promoting extra-pulmonary end-organ injury.
    • Organ injury can occur even without apparent acute lung injury.