Critical Care Medicine  |   May 2017
One-hit Models of Ventilator-induced Lung Injury: Benign Inflammation versus Inflammation as a By-product
Author Notes
  • From the Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Institute of Pharmacology and Toxicology, Aachen, Germany.
  • Corresponding article on page 766.
    Corresponding article on page 766.×
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    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Submitted for publication June 2, 2016. Accepted for publication January 12, 2017.
    Submitted for publication June 2, 2016. Accepted for publication January 12, 2017.×
  • Address correspondence to Dr. Uhlig: RWTH Aachen University, Institute of Pharmacology and Toxicology, Wendlingweg 2, 52074 Aachen, Germany. suhlig@ukaachen.de. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Basic Science / Critical Care / Respiratory System
Critical Care Medicine   |   May 2017
One-hit Models of Ventilator-induced Lung Injury: Benign Inflammation versus Inflammation as a By-product
Anesthesiology 5 2017, Vol.126, 909-922. doi:10.1097/ALN.0000000000001605
Anesthesiology 5 2017, Vol.126, 909-922. doi:10.1097/ALN.0000000000001605
Abstract

Background: One important explanation for the detrimental effects of conventional mechanical ventilation is the biotrauma hypothesis that ventilation may trigger proinflammatory responses that subsequently cause lung injury. This hypothesis has frequently been studied in so-called one-hit models (overventilation of healthy lungs) that so far have failed to establish an unequivocal link between inflammation and hypoxemic lung failure. This study was designed to develop a one-hit biotrauma model.

Methods: Mice (six per group) were ventilated for up to 7 h (positive end-expiratory pressure 2 cm H2O) and received 300 μl/h fluid support. Series_1: initial plateau pressures of 10, 24, 27, or 30 cm H2O. Series_2: ventilation with pressure release at 34 cm H2O and initial plateau pressure of 10, 24, 27, or 30 cm H2O. To study the significance of inflammation, the latter groups were also pretreated with the steroid dexamethasone.

Results: Within 7 h, 20 of 24 mice ventilated with plateau pressure of 27 cm H2O or more died of a catastrophic lung failure characterized by strongly increased proinflammatory markers and a precipitous decrease in pulmonary compliance, blood pressure, and oxygenation. Pretreatment with dexamethasone reduced inflammation, but prolonged median survival time by 30 min.

Conclusions: Our findings demonstrate a sharp distinction between ventilation with 24 cm H2O that was well tolerated and ventilation with 27 cm H2O that was lethal for most animals due to catastrophic lung failure. In the former case, inflammation was benign and in the latter, a by-product that only accelerated lung failure. The authors suggest that biotrauma—when defined as a ventilation-induced and inflammation-dependent hypoxemia—is difficult to study in murine one-hit models of ventilation, at least not within 7 h. (Anesthesiology 2017; 126:909-22)