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CRITICAL CARE AND TRAUMA

Pulmonary Cytokine Responses During Mechanical Ventilation of Noninjured Lungs With and Without End-Expiratory Pressure

Torsten Meier, MD^*, Alexandra Lange^*, Hilke Papenberg, MD^*, Malte Ziemann, MD^*, Christina Fentrop, PhD, Ulrike Uhlig, PhD, Peter Schmucker, MD^*, Stefan Uhlig, PhD, and Cordula Stamme, MD

From the *Department of Anesthesiology, University Medical Center Schleswig-Holstein, Campus Lübeck, Germany; Institute of Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany; and Research Group Cellular Pneumology, Research Center Borstel, Germany.

Address correspondence to Stefan Uhlig, PhD, Institute of Pharmacology and Toxicology, Universitätsklinikum Aachen, RWTH Aachen University, Wendlingweg 2, 52074 Aachen, Germany. Address e-mail to suhlig{at}ukaachen.de.

BACKGROUND: Positive end-expiratory pressure (PEEP) during mechanical ventilation may impose different degrees of stress on healthy lungs. On the assumption that stress is reflected by cytokine production, we performed a translational study investigating the effect of PEEP on bronchoalveolar and systemic mediator levels in isolated perfused mouse lungs (IPL) and in patients with healthy lungs.

METHODS: (Part I) IPL were ventilated with end-expiratory pressures of 0, 3, 6, or 10 cm H₂O and end-inspiratory pressure (EIP) levels of 10 or 25 cm H₂O. Interleukin (IL)-6 and macrophage inflammatory protein-2 concentrations in the venous effluate were monitored. (Part II) Patients (nonsmokers) scheduled for elective otorhinolaryngology surgery (duration >90 min) were randomized to receive either ventilation with zero end-expiratory pressure or PEEP (10 cm H₂O). Mediators in bronchoalveolar lavage, nuclear factor B, (NF-B)-activation in alveolar macrophages and circulating systemic mediators were monitored. Control patients underwent bronchoalveolar lavage after intubation.

RESULTS: In the IPL, mediator concentrations increased with increasing end-expiratory pressure at an EIP of 10 cm H₂O, but decreased at 25 cm H₂O EIP. In patients, bronchoalveolar IL-6, monocyte chemoattractant protein-1, and granulocyte monocyte-colony stimulating factor were increased by ventilation regardless of the PEEP level. IL-6 and IL-8 levels were moderately increased by PEEP but not zero end-expiratory pressure. Nuclear factor B DNA binding activity in alveolar macrophages and systemic mediator levels did not change.

CONCLUSIONS: On the basis of the premise that cytokine levels may indicate mechanical stress, our findings indicate that even low tidal volume ventilation causes some stress. PEEP is beneficial at high inspiratory pressure, but imposes moderate stress at low inspiratory pressure.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999